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Background: The cell development atlas of transition stage from late Carnegie to fetal development (7-9 weeks) remain unclear. It can be seen that the early period of human embryos (7-9 weeks) is a critical research gap. Therefore, we employed single‑cell RNA sequencing to identify cell types and elucidate differentiation relationships., Results: The single‑cell RNA sequencing analysis determines eighteen cell clusters in human embryos during the 7-9 weeks period. We uncover two distinct pathways of cellular development and differentiation. Initially, mesenchymal progenitor cells differentiated into osteoblast progenitor cells and neural stem cells, respectively. Neural stem cells further differentiated into neurons. Alternatively, multipotential stem cells differentiated into adipocyte, hematopoietic stem cells and neutrophil, respectively. Additionally, COL1A2-(ITGA1 + ITGB1) mediated the cell communication between mesenchymal progenitor cells and osteoblast progenitor cells. NCAM1-FGFR1 facilitated the cell communication between mesenchymal progenitor cells and neural stem cells. Notably, NCAM1-NCAM1 as a major contributor mediated the cell communication between neural stem cells and neurons. Moreover, CGA-FSHR simultaneously mediated the communication between multipotential stem cells, adipocyte, hematopoietic stem cells and neutrophil. Distinct cell clusters activated specific transcription factors such as HIC1, LMX1B, TWIST1, and et al., which were responsible for their specific functions. These coregulators, such as HOXB13, VSX2, PAX5, and et al., may mediate cell development and differentiation in human embryos., Conclusions: We provide the cell development atlas for human embryos (7-9 weeks). Two distinct cell development and differentiation pathways are revealed., (© 2024. The Author(s).)

Typical differential single-nucleus gene expression (snRNA-seq) analyses in Alzheimer's disease (AD) provide fixed snapshots of cellular alterations, making the accurate detection of temporal cell changes challenging. To characterize the dynamic cellular and transcriptomic differences in AD neuropathology, we apply the novel concept of RNA velocity to the study of single-nucleus RNA from the cortex of 60 subjects with varied levels of AD pathology. RNA velocity captures the rate of change of gene expression by comparing intronic and exonic sequence counts. We performed differential analyses to find the significant genes driving both cell type-specific RNA velocity and expression differences in AD, extensively compared these two transcriptomic metrics, and clarified their associations with multiple neuropathologic traits. The results were cross-validated in an independent dataset. Comparison of AD pathology-associated RNA velocity with parallel gene expression differences reveals sets of genes and molecular pathways that underlie the dynamic and static regimes of cell type-specific dysregulations underlying the disease. Differential RNA velocity and its linked progressive neuropathology point to significant dysregulations in synaptic organization and cell development across cell types. Notably, most of the genes underlying this synaptic dysregulation showed increased RNA velocity in AD subjects compared to controls. Accelerated cell changes were also observed in the AD subjects, suggesting that the precocious depletion of precursor cell pools might be associated with neurodegeneration. Overall, this study uncovers active molecular drivers of the spatiotemporal alterations in AD and offers novel insights towards gene- and cell-centric therapeutic strategies accounting for dynamic cell perturbations and synaptic disruptions., (© 2024. The Author(s).)

Blood-borne pathogens can cause systemic inflammatory response syndrome (SIRS) followed by protracted, potentially lethal immunosuppression. The mechanisms responsible for impaired immunity post-SIRS remain unclear. We show that SIRS triggered by pathogen mimics or malaria infection leads to functional paralysis of conventional dendritic cells (cDCs). Paralysis affects several generations of cDCs and impairs immunity for 3-4 weeks. Paralyzed cDCs display distinct transcriptomic and phenotypic signatures and show impaired capacity to capture and present antigens in vivo. They also display altered cytokine production patterns upon stimulation. The paralysis program is not initiated in the bone marrow but during final cDC differentiation in peripheral tissues under the influence of local secondary signals that persist after resolution of SIRS. Vaccination with monoclonal antibodies that target cDC receptors or blockade of transforming growth factor β partially overcomes paralysis and immunosuppression. This work provides insights into the mechanisms of paralysis and describes strategies to restore immunocompetence post-SIRS., Competing Interests: Declaration of interests M.H.L., I.C., and K.S. are listed as inventors on patents relating to Clec9A antibodies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Tissue engineering of exogenous skeletal muscle units (SMUs) through isolation of muscle satellite cells from muscle biopsies is a potential treatment method for acute volumetric muscle loss (VML). A current issue with this treatment process is the limited capacity for muscle stem cell (satellite cell) expansion in cell culture, resulting in a decreased ability to obtain enough cells to fabricate SMUs of appropriate size and structural quality and that produce native levels of contractile force. This study determined the impact of human recombinant irisin on the growth and development of three-dimensional (3D) engineered skeletal muscle. Muscle satellite cells were cultured without irisin (control) or with 50, 100, or 250 ng/mL of irisin supplementation. Light microscopy was used to analyze myotube formation with particular focus placed on the diameter and density of the monotubes during growth of the 3D SMU. Following the formation of 3D constructs, SMUs underwent measurement of maximum tetanic force to analyze contractile function, as well as immunohistochemical staining, to characterize muscle structure. The results indicate that irisin supplementation with 250 ng/mL significantly increased the average diameter of myotubes and increased the proliferation and differentiation of myoblasts in culture but did not have a consistent significant impact on force production. In conclusion, supplementation with 250 ng/mL of human recombinant irisin promotes the proliferation and differentiation of myotubes and has the potential for impacting contractile force production in scaffold-free tissue-engineered skeletal muscle.

Key Message: Overexpression of SlPRE3 is detrimental to the photosynthesis and alters plant morphology and root development. SlPRE3 interacts with SlAIF1/SlAIF2/SlPAR1/SlIBH1 to regulate cell expansion. Basic helix-loop-helix (bHLH) transcription factors play crucial roles as regulators in plant growth and development. In this study, we isolated and characterized SlPRE3, an atypical bHLH transcription factor gene. SlPRE3 exhibited predominant expression in the root and moderate expression in the senescent leaves. Comparative analysis with the wild type revealed significant differences in plant morphology in the 35S:SlPRE3 lines. These differences included increased internode length, rolling leaves with reduced chlorophyll accumulation, and elongated yet fewer adventitious roots. Additionally, 35S:SlPRE3 lines displayed elevated levels of GA 3 (gibberellin A3) and reduced starch accumulation. Furthermore, utilizing the Y2H (Yeast two-hybrid) and the BiFC (Bimolecular Fluorescent Complimentary) techniques, we identified physical interactions between SlPRE3 and SlAIF1 (ATBS1-interacting factor 1)/SlAIF2 (ATBS1-interacting factor 2)/SlPAR1 (PHYTOCHROME RAPIDLY REGULATED 1)/SlIBH1 (ILI1-binding bHLH 1). RNA-seq analysis of root tissues revealed significant alterations in transcript levels of genes involved in gibberellin metabolism and signal transduction, cell expansion, and root development. In summary, our study sheds light on the crucial regulatory role of SlPRE3 in determining plant morphology and root development., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cancer stem cells are the root cause of cancer, which, in essence, is a developmental disorder. All- trans retinoic acid (ATRA) signaling via ligand-activation of the retinoic acid receptors (RARs) plays a crucial role in tissue patterning and development during mammalian embryogenesis. In adults, active RARγ maintains the pool of hematopoietic stem cells, whereas active RARα drives myeloid cell differentiation. Various findings have revealed that ATRA signaling is deregulated in many cancers. The enzymes for ATRA synthesis are downregulated in colorectal, gastric, lung, and oropharyngeal cancers. ATRA levels within breast, ovarian, pancreatic, prostate, and renal cancer cells were lower than within their normal counterpart cells. The importance is that 0.24 nM ATRA activates RARγ (for stem cell stemness), whereas 100 times more is required to activate RARα (for differentiation). Moreover, RARγ is an oncogene regarding overexpression within colorectal, cholangiocarcinoma, hepatocellular, ovarian, pancreatic, and renal cancer cells. The microRNA (miR) 30a-5p downregulates expression of RARγ, and miR-30a/miR-30a-5p is a tumor suppressor for breast, colorectal, gastric, hepatocellular, lung, oropharyngeal, ovarian, pancreatic, prostate, and renal cancer. These complementary findings support the view that perturbations to ATRA signaling play a role in driving the abnormal behavior of cancer stem cells. Targeting ATRA synthesis and RARγ has provided promising approaches to eliminating cancer stem cells because such agents have been shown to drive cell death.

Comprehensive utilization of cottonseeds is limited by the presence of pigment glands and its inclusion gossypol. The ideal cotton has glandless seeds but a glanded plant, a trait found in only a few Australian wild cotton species, including Gossypium bickii. Introgression of this trait into cultivated species has proved to be difficult. Understanding the biological processes toward pigment gland morphogenesis and the associated underlying molecular mechanisms will facilitate breeding of cultivated cotton varieties with the trait of glandless seeds and glanded plant. In this study, single-cell RNA sequencing (scRNA-seq) was performed on 12 222 protoplasts isolated from cotyledons of germinating G. bickii seeds 48 h after imbibition. Clustered into 14 distinct clusters unsupervisedly, these cells could be grouped into eight cell populations with the assistance of known cell marker genes. The pigment gland cells were well separated from others and could be separated into pigment gland parenchyma cells, secretory cells, and apoptotic cells. By integrating the pigment gland cell developmental trajectory, transcription factor regulatory networks, and core transcription factor functional validation, we established a model for pigment gland formation. In this model, light and gibberellin were verified to promote the formation of pigment glands. In addition, three novel genes, GbiERF114 (ETHYLENE RESPONSE FACTOR 114), GbiZAT11 (ZINC FINGER OF ARABIDOPSIS THALIANA 11), and GbiNTL9 (NAC TRANSCRIPTION FACTOR-LIKE 9), were found to affect pigment gland formation. Collectively, these findings provide new insights into pigment gland morphogenesis and lay the cornerstone for future cotton scRNA-seq investigations., (Copyright © 2023 The Author. Published by Elsevier Inc. All rights reserved.)

Rationale: TOX is a DNA-binding factor required for the development of multiple immune cells and the formation of lymph nodes. However, the temporal regulation mode of TOX on NK cell development and function needs to be further explored. Methods: To investigate the role of TOX in NK cells at distinct developmental phases, we deleted TOX at the hematopoietic stem cell stage ( Vav-Cre ), NK cell precursor ( CD122-Cre ) stage and late NK cell developmental stage ( Ncr1-Cre ), respectively. Flow cytometry was used to detect the development and functional changes of NK cell when deletion of TOX. RNA-seq was used to assess the differences in transcriptional expression profile of WT and TOX-deficient NK cells. Published Chip-seq data was exploited to search for the proteins directly interact with TOX in NK cells. Results: The deficiency of TOX at the hematopoietic stem cell stage severely retarded NK cell development. To a less extent, TOX also played an essential role in the physiological process of NKp cells differentiation into mature NK cells. Furthermore, the deletion of TOX at NKp stage severely impaired the immune surveillance function of NK cells, accompanied by down-regulation of IFN-γ and CD107a expression. However, TOX is dispensable for mature NK cell development and function. Mechanistically, by combining RNA-seq data with published TOX ChIP-seq data, we found that the inactivation of TOX at NKp stage directly repressed the expression of Mst1, an important intermediate kinase in Hippo signaling pathway. Mst1 deficient at NKp stage gained the similar phenotype with Tox fl/fl CD122 Cre mice. Conclusion: In our study, we conclude that TOX coordinates the early mouse NK cell development at NKp stage by maintaining the expression of Mst1. Moreover, we clarify the different dependence of the transcription factor TOX in NK cells biology., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) regulates mammalian ovarian follicle growth and maturation; however, its effect on luteinized granulosa cells (LGCs) in sheep ovarian follicles remains unknown. Here we explored the regulatory role of LGC functions and steroid hormone synthesis by BAMBI. Multiple sequence alignment revealed that the sheep BAMBI gene sequence was relatively conserved. Sheep LGCs were strongly positive for BAMBI. LGC proliferation increased when BAMBI was silenced and decreased when BAMBI was overexpressed. After BAMBI overexpression, the expression of CASP3, CASP8, CASP9, and BAX significantly increased, whereas that of BCL2 and the ratio of BCL2/BAX expression decreased. The opposite was observed after BAMBI silencing. CDKN1A, CCND1, and CCND2 were downregulated with BAMBI overexpression and upregulated with BAMBI silencing. Expression of steroid hormone-related genes (CYP11A1, STAR, and 3BHSD), except CYP19A1, significantly increased after BAMBI overexpression. Moreover, estrogen and progesterone secretion increased after BAMBI overexpression and decreased after BAMBI interference. The effect of the exogenous addition of bone morphogenetic protein 2 (BMP2) on GCs was similar to that of BAMBI overexpression. In conclusion, BAMBI can regulate the proliferation and steroid hormone synthesis of sheep LGCs, and BMP2 can affect LGCs as an activator of BAMBI. These findings provide a basis for further research on the physiological role of BAMBI., (© 2023 Wiley Periodicals LLC.)

Clipping of the histone H3 N-terminal tail has been implicated in multiple fundamental biological processes for a growing list of eukaryotes. H3 clipping, serving as an irreversible process to permanently remove some post-translational modifications (PTMs), may lead to noticeable changes in chromatin dynamics or gene expression. The eukaryotic model organism Tetrahymena thermophila is among the first few eukaryotes that exhibits H3 clipping activity, wherein the first six amino acids of H3 are cleaved off during vegetative growth. Clipping only occurs in the transcriptionally silent micronucleus of the binucleated T. thermophila , thus offering a unique opportunity to reveal the role of H3 clipping in epigenetic regulation. However, the physiological functions of the truncated H3 and its protease(s) for clipping remain elusive. Here, we review the major findings of H3 clipping in T. thermophila and highlight its association with histone modifications and cell cycle regulation. We also summarize the functions and mechanisms of H3 clipping in other eukaryotes, focusing on the high diversity in terms of protease families and cleavage sites. Finally, we predict several protease candidates in T. thermophila and provide insights for future studies., Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-022-00151-0., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Ocean University of China 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Gonadal cell lines possess the abilities of self-renewal and differentiation, being used as an efficient tool to analyzing the genes' functions involved in sex differentiation and gametogenesis. Although some significant achievements have been obtained in the gonadal cells' culture or manipulation across multiple phyla including teleost and mammals, there is limited study on gonadal cell manipulation in turtles. In this study, we established a new ovarian cell line from the young Asian yellow pond turtle ( Mauremys mutica ), which exhibited a normal diploid karyotype with high alkaline phosphatase activity. The cell line, designated as YTO2, was then characterized through the analysis of gene expression profiles. The transcriptome analysis and the reverse transcription polymerase chain reaction (RT-PCR) showed that the cells expressed germline genes such as tdrd7 , nanos1 , klf5 , igtb1 , hsd17b4 and rad51 . Moreover, the immunostaining showed that the germ cell markers, Tdrd7 and Rad51 proteins, were detected predominant in cytoplasm of perinuclear region, while proliferation marker, PCNA, was dominantly observed in the nuclei of cultured cells. Intriguingly, the cells could respond to the retinoic acid induction with significantly increasing the expression level of some meiosis genes, including vasa , dazl , figla , and dmc1 . Furthermore, YTO2 cells could be efficiently transfected with the pHBAd-BHG-EGFP adenovirus and properly expressed the exogenous genes. To sum up, an ovarian cell line of the Asian yellow pond turtle had been established and could be stably propagated under in vitro culture condition, as well as being capable of efficiently expressing the exogenous gene tdrd7 . This cell line would provide a valuable tool to elaborate the molecular mechanisms behind germ cells development, differentiation and oogenesis in the turtle, even in reptiles.

Oligodendrocytes are the glial cells responsible for the formation of myelin around axons of the central nervous system (CNS). Myelin is an insulating layer that allows electrical impulses to transmit quickly and efficiently along neurons. If myelin is damaged, as in chronic demyelinating disorders such as multiple sclerosis (MS), these impulses slow down. Remyelination by oligodendrocytes is often ineffective in MS, in part because of the failure of oligodendrocyte precursor cells (OPCs) to differentiate into mature, myelinating oligodendrocytes. The process of oligodendrocyte differentiation is tightly controlled by several regulatory networks involving transcription factors, intracellular signaling pathways, and extrinsic cues. Understanding the factors that regulate oligodendrocyte development is essential for the discovery of new therapeutic strategies capable of enhancing remyelination. Over the past decade, microRNAs (miRNAs) have emerged as key regulators of oligodendrocyte development, exerting effects on cell specification, proliferation, differentiation, and myelination. This article will review the role of miRNAs on oligodendrocyte biology and discuss their potential as promising therapeutic tools for remyelination., (© 2022 International Society for Neurochemistry.)

The tongue is a unique muscular organ situated in the oral cavity where it is involved in taste sensation, mastication, and articulation. As a barrier organ, which is constantly exposed to environmental pathogens, the tongue is expected to host an immune cell network ensuring local immune defence. However, the composition and the transcriptional landscape of the tongue immune system are currently not completely defined. Here, we characterised the tissue-resident immune compartment of the murine tongue during development, health and disease, combining single-cell RNA-sequencing with in situ immunophenotyping. We identified distinct local immune cell populations and described two specific subsets of tongue-resident macrophages occupying discrete anatomical niches. Cx3cr1 + macrophages were located specifically in the highly innervated lamina propria beneath the tongue epidermis and at times in close proximity to fungiform papillae. Folr2 + macrophages were detected in deeper muscular tissue. In silico analysis indicated that the two macrophage subsets originate from a common proliferative precursor during early postnatal development and responded differently to systemic LPS in vivo. Our description of the under-investigated tongue immune system sets a starting point to facilitate research on tongue immune-physiology and pathology including cancer and taste disorders., Competing Interests: EL, KZ, LW, DD, CK, CF, SJ, AH, WS, SD, TC, AL, AM No competing interests declared, SY Reviewing editor, eLife, (© 2022, Lyras et al.)

Cellular development is orchestrated by evolutionarily conserved signaling pathways, which are often pleiotropic and involve intra- and interpathway epistatic interactions that form intricate, complex regulatory networks. Cryptococcus species are a group of closely related human fungal pathogens that grow as yeasts yet transition to hyphae during sexual reproduction. Additionally, during infection they can form large, polyploid titan cells that evade immunity and develop drug resistance. Multiple known signaling pathways regulate cellular development, yet how these are coordinated and interact with genetic variation is less well understood. Here, we conducted quantitative trait locus (QTL) analyses of a mapping population generated by sexual reproduction of two parents, only one of which is unisexually fertile. We observed transgressive segregation of the unisexual phenotype among progeny, as well as a large-cell phenotype under mating-inducing conditions. These large-cell progeny were found to produce titan cells both in vitro and in infected animals. Two major QTLs and corresponding quantitative trait genes (QTGs) were identified: RIC8 (encoding a guanine-exchange factor) and CNC06490 (encoding a putative Rho-GTPase activator), both involved in G protein signaling. The two QTGs interact epistatically with each other and with the mating-type locus in phenotypic determination. These findings provide insights into the complex genetics of morphogenesis during unisexual reproduction and pathogenic titan cell formation and illustrate how QTL analysis can be applied to identify epistasis between genes. This study shows that phenotypic outcomes are influenced by the genetic background upon which mutations arise, implicating dynamic, complex genotype-to-phenotype landscapes in fungal pathogens and beyond., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Dendritic cells (DC) have a key role in the initiation and progression of inflammatory arthritis (IA). In this study, we identified a DC population that derive from monocytes, characterized as CD209/CD14 + DC, expressing classical DC markers (HLADR, CD11c) and the Mo-DC marker (CD209), while also retaining the monocytic marker CD14. This CD209/CD14 + DC population is present in the circulation of Healthy Control (HC), with increased frequency in Rheumatoid Arthritis (RA) and Psoriatic arthritic (PsA) patients. We demonstrate, for the first time, that circulatory IA CD209/CD14 + DC express more cytokines (IL1β/IL6/IL12/TNFα) and display a unique chemokine receptor expression and co-expression profiles compared to HC. We demonstrated that CD209/CD14 + DC are enriched in the inflamed joint where they display a unique inflammatory and maturation phenotype, with increased CD40 and CD80 and co-expression of specific chemokine receptors, displaying unique patterns between PsA and RA. We developed a new protocol of magnetic isolation and expansion for CD209 + DC from blood and identified transcriptional differences involved in endocytosis/antigen presentation between RA and PsA CD209 + DC. In addition, we observed that culture of healthy CD209 + DC with IA synovial fluid (SF), but not Osteoarthritis (OA) SF, was sufficient to induce the development of CD209/CD14 + DC, leading to a poly-mature DC phenotype. In addition, differential effects were observed in terms of chemokine receptor and chemokine expression, with healthy CD209 + DC displaying increased expression/co-expression of CCR6, CCR7, CXCR3, CXCR4 and CXCR5 when cultured with RA SF, while an increase in the chemokines CCR3, CXCL10 and CXCL11 was observed when cultured with PsA SF. This effect may be mediated in part by the observed differential increase in chemokines expressed in RA vs PsA SF. Finally, we observed that the JAK/STAT pathway, but not the NF-κB pathway (driven by TNFα), regulated CD209/CD14 + DC function in terms of activation, inflammatory state, and migratory capacity. In conclusion, we identified a novel CD209/CD14 + DC population, which is active in the circulation of RA and PsA, an effect potentiated once they enter the joint. Furthermore, we demonstrated that JAK/STAT inhibition can be used as a therapeutic strategy to decrease the inflammatory state of the pathogenic CD209/CD14 + DC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marzaioli, Canavan, Floudas, Flynn, Mullan, Veale and Fearon.)

In most human primary cancers, the expression, or telomerase activity, of telomerase reverse transcriptase ( TERT ) is detectable. However, the mechanism of TERT activity within oncogenesis of thyroid cancer remains largely unknown. In this study, we identified miR-195-5p as having involvement in cell proliferation, apoptosis, and invasion in human thyroid cancer. MTT was used to measure cell proliferation, Transwell chamber was used to measure invasion. Western blotting was used to detect the expressions of TERT, PCNA, and Ki67. Target gene prediction software predicted that TERT may be the target gene of miR-195-5p. Luciferase reporting system was used to identify the targeting relationship. A significant increase of in TERT expression was observed by immunohistochemistry compared with normal tissue, however, a decrease in miR-195-5p expression using qRT-PCRand western blot compared with normal cells. Functional analysis demonstrates that miR-195-5p negatively correlated with TERT and inhibited TERT expression through its interaction with the TERT 3'-untranslatedregion (3'-UTR). Overexpression of miR-195-5p was shown to inhibit proliferation and invasion, and promote apoptosis of CAL-62 thyroid cancer cells. miR-195-5p-mediatedeffects were rescued by the overexpression of TERT . Altogether, our data demonstrate that miR-195-5p regulates cell proliferation, apoptosis, and invasion in human thyroid cancer via TERT , providing evidence of a new potential therapeutic target for further investigation.

In vivo monitoring of rice ( Oryza sativa L.) seed germination and seedling growth under general conditions in closed Petri dishes containing agar base medium at room temperature (temperature = 24.5 ± 1 °C, relative humidity = 76 ± 7% (average ± standard deviation)), and induced degenerated callus formation with plant growth regulator, were performed using short-wavelength near-infrared spectroscopy and aquaphotomics over A period of 26 days. The results of spectral analysis suggest changes in water absorbances due to the production of common metabolites, as well as increases in biomass and the sizes of the samples. Quantitative models built to predict the day of the development provided better accuracy for rice seedlings growth compared to callus formation. Eight common water bands were identified as presenting prominent changes in the absorbance pattern. The water matrix of only rice seedlings showed three developmental stages: firstly expressing a predominantly weakly hydrogen-bonded state, then a more strongly hydrogen-bonded state, and then, again, a weakly hydrogen-bonded state at the end. In rice callus induction and proliferation, no similar change in water absorbance pattern was observed. The presented findings indicate the potential of aquaphotomics for the in vivo detection of degeneration in cell development.

Follicular regulatory T (Tfr) cells are recently found to be a special subgroup of regulatory T (Treg) cells. Tfr cells play an important role in regulating the germinal center (GC) response, especially modulating follicular helper T (Tfh) cells and GC-B cells, thereby affecting the production of antibodies. Tfr cells are involved in the generation and development of many immune-related and inflammatory diseases. This article summarizes the advances in several aspects of Tfr cell biology, with special focus on definition and phenotype, development and differentiation, regulatory factors, functions, and interactions with T/B cells and molecules involved in performance and regulation of Tfr function. Finally, we highlight the current understanding of Tfr cells involvement in autoimmunity and alloreactivity, and describe some drugs targeting Tfr cells. These latest studies have answered some basic questions in Tfr cell biology and explored the roles of Tfr cells in immune-mediated diseases., (©2021 Society for Leukocyte Biology.)

TET proteins are DNA demethylases that can oxidize 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC) and other oxidized mC bases (oxi-mCs). Importantly, TET proteins govern cell fate decisions during development of various cell types by activating a cell-specific gene expression program. In this review, we focus on the role of TET proteins in T-cell lineage specification. We explore the multifaceted roles of TET proteins in regulating gene expression in the contexts of T-cell development, lineage specification, function, and disease. Finally, we discuss the future directions and experimental strategies required to decipher the precise mechanisms employed by TET proteins to fine-tune gene expression and safeguard cell identity., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Circular RNAs (circRNAs) have been reported to be related to the development of human cancers. However, the function of circ-FOXM1 in non-small cell lung cancer (NSCLC) was largely unknown. Here, we revealed the role and functional mechanism of circ-FOXM1 in NSCLC progression. The relative expression of circ-FOXM1, microRNA-149-5p (miR-149-5p), and autophagy-related 5 (ATG5) was determined by quantitative real-time polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assay were employed to assess cell viability, apoptosis, and migration, respectively. The relative protein expression was detected by western blot. Furthermore, mouse xenograft was carried out to analyze the effect of circ-FOXM1 on tumor growth in vivo . In addition, the interaction between miR-149-5p and circ-FOXM1 or ATG5 was predicted by Starbase3.0 and confirmed by the dual-luciferase reporter assay and RNA pull-down assay. Circ-FOXM1 and ATG5 levels were upregulated, while the miR-149-5p level was downregulated in NSCLC tissues and cells. Circ-FOXM1 knockdown suppressed NSCLC cell viability, migration, and autophagy, and induced cell apoptosis. Interestingly, circ-FOXM1 targeted miR-149-5p to upregulate the ATG5 level. Moreover, circ-FOXM1 exerted function through repressing miR-149-5p expression, and miR-149-5p exerted function via inhibiting ATG5 expression. Our results suggested that circ-FOXM1 knockdown attenuated the development of NSCLC through modulating the miR-149-5p/ATG5 axis, providing a theoretical basis for the therapy of NSCLC.

Background: In epigenetics, the change of the combination of histone modifications at the same genomic location during cell differentiation is of great interest for understanding the function of these modifications and their combinations. Besides analyzing them locally for individual genomic locations or globally using correlations between different cells types, intermediate level analyses of these changes are of interest. More specifically, the different distributions of these combinations for different cell types, respectively, are compared to gain new insights., Results and Discussion: We propose a new tool called 'Masakari' that allows segmenting genomes based on lists of ranges having a certain property, e.g., peaks describing histone modifications. It provides a graphical user interface allowing to select all data sets and setting all parameters needed for the segmentation process. Moreover, the graphical user interface provides statistical graphics allowing to assess the quality and suitability of the segmentation and the selected data., Conclusion: Masakari provides statistics based visualizations and thus fosters insights into the combination of histone modification marks on genome ranges, and the differences of the distribution of these combinations between different cell types.

As an essential and fundamental process of life, cell development involves large-scale reorganization of the 3D genome architecture, which forms the basis of gene regulation. Here, a landscape-switching model is developed to explore the microscopic chromosomal structural origin of embryonic stem cell (ESC) differentiation and somatic cell reprogramming. It is shown that chromosome structure exhibits significant compartment-switching in the unit of topologically associating domain. It is found that the chromosome during differentiation undergoes monotonic compaction with spatial repositioning of active and inactive chromosomal loci toward the chromosome surface and interior, respectively. In contrast, an overexpanded chromosome, which exhibits universal localization of loci at the chromosomal surface with erasing the structural characteristics formed in the somatic cells, is observed during reprogramming. An early distinct differentiation pathway from the ESC to the terminally differentiated cell, giving rise to early bifurcation on the Waddington landscape for the ESC differentiation is suggested. The theoretical model herein including the non-equilibrium effects, draws a picture of the highly irreversible cell differentiation and reprogramming processes, in line with the experiments. The predictions provide a physical understanding of cell differentiation and reprogramming from the chromosomal structural and dynamical perspective and can be tested by future experiments., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley‐VCH GmbH.)

Essential genes are those whose loss of function compromises organism viability or results in profound loss of fitness. Recent gene-editing technologies have provided new opportunities to characterize essential genes. Here, we present an integrated analysis that comprehensively and systematically elucidates the genetic and regulatory characteristics of human essential genes. First, we found that essential genes act as 'hubs' in protein-protein interaction networks, chromatin structure and epigenetic modification. Second, essential genes represent conserved biological processes across species, although gene essentiality changes differently among species. Third, essential genes are important for cell development due to their discriminate transcription activity in embryo development and oncogenesis. In addition, we developed an interactive web server, the Human Essential Genes Interactive Analysis Platform (http://sysomics.com/HEGIAP/), which integrates abundant analytical tools to enable global, multidimensional interpretation of gene essentiality. Our study provides new insights that improve the understanding of human essential genes., (© The Author(s) 2019. Published by Oxford University Press.)

Plant cell walls constitute the extracellular matrix surrounding plant cells and are composed mainly of polysaccharides. The chemical makeup of the primary plant cell wall, and specifically, the abundance, localization and arrangement of the constituting polysaccharides are intimately linked with growth, morphogenesis and differentiation in plant cells. Visualization of the cell wall components is, therefore, a crucial tool in plant cell developmental studies. In this technical update, we present protocols for fluorescence visualization of cellulose and pectin in selected plant tissues and illustrate examples of some of the available labels that hold promise for live imaging of plant cell wall expansion and morphogenesis., (© 2020 Royal Microscopical Society.)

Plasmacytoid dendritic cells (pDCs) are a unique subset of dendritic cells specialised in secreting high levels of type I interferons. pDCs play a crucial role in antiviral immunity and have been implicated in the initiation and development of many autoimmune and inflammatory diseases. This review summarises the latest advances in recent years in several aspects of pDC biology, with special focus on pDC heterogeneity, pDC development via the lymphoid pathway, and newly identified proteins/pathways involved in pDC trafficking, nucleic acid sensing and interferon production. Finally, we also highlight the current understanding of pDC involvement in autoimmunity and alloreactivity, and opportunities for pDC-targeting therapies in these diseases. These new insights have contributed to answers to several fundamental questions remaining in pDC biology and may pave the way to successful pDC-targeting therapy in the future., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Proliferating cells must coordinate central metabolism with the cell cycle. How central energy metabolism regulates bacterial cell cycle functions is not well understood. Our forward genetic selection unearthed the Krebs cycle enzyme citrate synthase (CitA) as a checkpoint regulator controlling the G 1 →S transition in the polarized alpha-proteobacterium Caulobacter crescentus , a model for cell cycle regulation and asymmetric cell division. We find that loss of CitA promotes the accumulation of active CtrA, an essential cell cycle transcriptional regulator that maintains cells in G 1 -phase, provided that the (p)ppGpp alarmone is present. The enzymatic activity of CitA is dispensable for CtrA control, and functional citrate synthase paralogs cannot replace CitA in promoting S-phase entry. Our evidence suggests that CitA was appropriated specifically to function as a moonlighting enzyme to link central energy metabolism with S-phase entry. Control of the G 1 -phase by a central metabolic enzyme may be a common mechanism of cellular regulation., Competing Interests: MB, JP, VG, LD, GM, SR, PV No competing interests declared, (© 2020, Bergé et al.)

Agmatinase is known as a metalloenzyme which hydrolyzes agmatine to produce urea and putrescine, being crucial in the alternative pathway to produce polyamines. In this study, an agmatinase-like protein (AGM-1) (NCU 01348) in the filamentous fungus Neurospora crassa is reported. Purified AGM-1 from N. crassa displays enzymatic activity hydrolyzing agmatine; therefore, it can be considered as an agmatinase-like protein. However, its role in the alternative pathway to produce polyamines apparently is not its main function since only a slight reduction of polyamines concentration was detected in the Δagm-1 het strain. Moreover, the null mutant Δagm-1 (homokaryon strain) was unable to grow and the deficiency of agm-1 in the heterokaryon strain provoked a decrease in elongation rate, conidia and biomass production, despite of having de constitutive pathway via the ornithine decarboxylase (ODC). Additionally, mature hyphae of the Δagm-1 het strain presented unusual apical branching and a disorganized Spitzenkörper (Spk). Trying to reveal the role of AGM-1in N. crassa, the protein was tagged with GFP and interestingly the dynamics and intracellular localization of AGM-1 closely resembles the F-actin population. This finding was further examined in order to elucidate if AGM-1is in a close association with F-actin. Since polyamines, among them agmatine, have been reported to act as stabilizers of actin filaments, we evaluated in vitro G-actin polymerization in the presence of agmatine and the effect of purified AGM-1 from N. crassa on these polymerized actin filaments. It was found that polymerization of actin filaments increases in the presence of agmatine and the addition of purified AGM-1 from N. crassa depolymerizes these actin filaments. Also, it was determined that an intact substrate binding site of the enzyme is necessary for the localization pattern of the native AGM-1. These results suggest that in N. crassa AGM-1 has a close association with the F-actin population via its substrate agmatine, playing an essential role during cell development., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Scope: Four and a half LIM domain protein 2 (FHL2) is a LIM domain protein expressed in muscle tissue whose deletion is causative of myopathies. Although FHL2 has a confirmed important role in muscle development, its autophagy-related function in muscle differentiation has not been fully determined. Methods: C2C12 cells were treated with FHL2-konwdown or FHL2-overexpression. The morphology of C2C12 cells was observed by transmission electron microscopy. The mRNA and protein abundances of muscle related genes and autophagy related genes were measured by RT-PCR and western blot. Immunofluorescence and co-immunoprecipitation assay were used to verify the interaction between FHL2 and LC3 protein. Results: FHL2 silencing reduced LC3-Ⅱ protein expression and the amount of LC3 that co-immunoprecipitated with FHL2, indicating that FHL2 interacts with LC3-Ⅱ in the formation of autophagosomes. Moreover, the expression of muscle development marker genes such as MyoD1 and MyoG was lower in FHL2-silenced C2C12 cells but not in FHL2-overexpressing C2C12 cells. Electron microscopy analysis revealed large empty autophagosomes in FHL2-silenced myoblasts, while flow cytometry suggested that FHL2 silencing made cells more vulnerable to staurosporine-induced cell death. Conclusion: These results suggest that FHL2 interacts with LC3-Ⅱ in autophagosome formation to regulate the development of muscle cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Single cell experimental techniques now allow us to quantify gene expression in up to thousands of individual cells. These data reveal the changes in transcriptional state that occur as cells progress through development and adopt specialized cell fates. In this chapter we describe in detail how to use our network inference algorithm (PIDC)-and the associated software package NetworkInference.jl-to infer functional interactions between genes from the observed gene expression patterns. We exploit the large sample sizes and inherent variability of single cell data to detect statistical dependencies between genes that indicate putative (co-)regulatory relationships, using multivariate information measures that can capture complex statistical relationships. We provide guidelines on how best to combine this analysis with other complementary methods designed to explore single cell data, and how to interpret the resulting gene regulatory network models to gain insight into the processes regulating cell differentiation.

Background: Patients with X-linked hyper-IgM syndrome caused by CD40 ligand (CD40L) deficiency often present with episodic, cyclic, or chronic neutropenia, suggesting abnormal neutrophil development in the absence of CD40L-CD40 interaction. However, even when not neutropenic and despite immunoglobulin replacement therapy, CD40L-deficient patients are susceptible to life-threatening infections caused by opportunistic pathogens, suggesting impaired phagocyte function and the need for novel therapeutic approaches., Objectives: We sought to analyze whether peripheral neutrophils from CD40L-deficient patients display functional defects and to explore the in vitro effects of recombinant human IFN-γ (rhIFN-γ) on neutrophil function., Methods: We investigated the microbicidal activity, respiratory burst, and transcriptome profile of neutrophils from CD40L-deficient patients. In addition, we evaluated whether the lack of CD40L in mice also affects neutrophil function., Results: Neutrophils from CD40L-deficient patients exhibited defective respiratory burst and microbicidal activity, which were improved in vitro by rhIFN-γ but not soluble CD40L. Moreover, neutrophils from patients showed reduced CD16 protein expression and a dysregulated transcriptome suggestive of impaired differentiation. Similar to CD40L-deficient patients, CD40L knockout mice were found to have impaired neutrophil responses. In parallel, we demonstrated that soluble CD40L induces the promyelocytic cell line HL-60 to proliferate and mature by regulating the expression of genes of the same Gene Ontology categories (eg, cell differentiation) when compared with those dysregulated in peripheral blood neutrophils from CD40L-deficient patients., Conclusion: Our data suggest a nonredundant role of CD40L-CD40 interaction in neutrophil development and function that could be improved in vitro by rhIFN-γ, indicating a potential novel therapeutic application for this cytokine., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Recent studies have identified CD49a + Eomes - and CD49a + Eomes + subsets of tissue-resident NK (trNK) cells in different organs of the mouse. However, the characteristics of CD49a + Eomes -/+ NK cell development and the regulation of Eomes expression in NK cells remain unclear. Here, we established an in vitro cytokine-based feeder-free system in which bone marrow progenitor cells differentiate into CD49a + NK cells. IL-15 was identified as being the key cytokine in this system that supported the development and maintenance of CD49a + NK cells. The CD49a + NK cells generated were Eomes - CD49b - and shared the same phenotype as hepatic trNK cells. IL-4 induced the expression of Eomes in generated NK cells and converted them into CD49a + Eomes + cells, which were phenotypically and functionally similar to uterine trNK cells. Moreover, the IL-4/STAT6 axis was identified as being important in the generation of CD49a + Eomes + induced NK cells. Collectively, these studies describe an approach to generate CD49a + Eomes -/+ subsets of NK cells and demonstrate important roles for IL-15 and IL-4 in the differentiation of these cells. These findings have potential for developmental research underlying the generation of different subsets of NK cells and the application of adoptive NK cell transfer therapies.

Nuclear factor κB (NF-κB) exhibits an important role in inflammation and tumorigenesis. The key regulatory protein of the pathway, RELB Proto-Oncogene, NF-KB Subunit (relB), is overexpressed and associated with the pathogenesis of a variety of malignant tumors. However, the molecular features and clinical signature of relB expression in gliomas remains to be elucidated. The present study obtained the raw sequencing data of 325 glioma samples of all grades from the Chinese Glioma Genome Atlas (CGGA) database and human glioma cell line (LN229) from the Chinese Academy of Sciences cell bank. Cell proliferation, invasion and wound healing assays were used for functional annotation of relB. Western blot analysis was used for validating the protein expression of relB, matrix metalloproteinase (MMP)-2 and MMP-9 in a further 77 glioma samples. In Diffuse Glioma data, relB expression was associated with glioma grade, demonstrated a mesenchymal subtype preference and cell development association. The downregulation of relB expression inhibited glioma cell migration and invasion by regulating the MMPs in vitro . relB expression was independently associated with grade and prognosis of grade III and grade IV gliomas, suggesting that relB is a novel biomarker with therapeutic potential for predicting prognosis in glioma.

MicroRNAs are small non-coding RNAs that can modulate gene expression at posttranscriptional level, and they participate in almost all important biological processes. Immune system is elaborately regulated to maintain the equilibrium between immunity and tolerance. Recent studies have revealed significant functions of microRNAs in the maintenance of immune homeostasis using both cell and transgenic mouse models. In collaboration with various transcriptional factors and cytokines, microRNAs constitute an effective and flexible regulatory network governing the development and activation of immune cells; as well as maintenance of immune tolerance. In this review, microRNAs involved in T cell development, proliferation, and lineage differentiation will be summarized. Based on current knowledge, the function of microRNAs in establishing and maintaining immune tolerance will also be discussed in relation to determining the outcome of allograft transplantation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The coordinated control of Ca 2+ signaling is essential for development in eukaryotes. Cyclic nucleotide-gated channel (CNGC) family members mediate Ca 2+ influx from cellular stores in plants (Charpentier et al., 2016; Gao et al., 2016; Frietsch et al., 2007; Urquhart et al., 2007). Here, we report the unusual genetic behavior of a quantitative gain-of-function CNGC mutation ( brush ) in Lotus japonicus resulting in a leaky tetrameric channel. brush resides in a cluster of redundant CNGCs encoding subunits which resemble metazoan voltage-gated potassium (Kv1-Kv4) channels in assembly and gating properties. The recessive mongenic brush mutation impaired root development and infection by nitrogen-fixing rhizobia. The brush allele exhibited quantitative behavior since overexpression of the cluster subunits was required to suppress the brush phenotype. The results reveal a mechanism by which quantitative competition between channel subunits for tetramer assembly can impact the phenotype of the mutation carrier.

The aim of the present study was to identify the differentially expressed genes (DEGs) that are induced by the silencing of transforming growth factor-β-activated kinase 1 ( TAK1 ) in bladder cancer cells and to analyze the potential biological effects. Dataset GSE52452 from mutant fibroblast growth factor receptor 3 ( FGFR3 ) bladder cancer cells transfected with control siRNA or TAK1 -specific siRNA was downloaded from Gene Expression Omnibus. The DEGs between the two groups were identified using Limma package following data pre-processing by Affy in Bioconductor. Enrichment analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Discovery, followed by functional annotation using TRANSFAC, TSGene and TAG databases. Integrated networks were constructed by Cytoscape and sub-networks were extracted employing BioNet, followed by enrichment analysis of DEGs in the sub-network. A total of 43 downregulated and 21 upregulated genes were obtained. The downregulated genes were enriched in five pathways, including NOD-like receptor signaling pathway and functions related to cellular response. The upregulated genes were associated with cellular developmental processes. Transcription factor EGR1 and 9 tumor-associated genes were screened from the DEGs. Among the DEGs, 10 hub nodes may represent important roles in the complex metabolic network, including EGFR , CYP3A5 , MAP3K7 , GSTA1 , PTHLH , ALDH1A1 , KCND2 , EGR1 , ARRB1 and ITPR1 . Additionally, EGFR was correlated with ERBB2 , GRB2 and PIK3R1 , and these were enriched in ErbB signaling pathway and various cancer-associated pathways. Silencing TAK1 may decrease cellular response to chemical stimulus via downregulating CYP3A5 , MAP3K7 , GSTA1 , ALDH1A1 , ARRB1 and ITPR1 ; increase cancer cell development via upregulating EGFR , EGR1 and PTHLH ; and regulate cancer metastasis through EGFR , ERBB2 , GRB2 and PIK3R1 .

There is increasing evidence showing specific roles of microRNA in cell differentiation and cancer progression. Here we examine miRNA profiles during maturation of monocytes and bone marrow-derived dendritic cells (BMDCs) in human and mouse, respectively. We have identified significant changes of various miRNA expression during monocyte and BMDC monocyte development via miRNA microarrays, confirmed by quantitative PCR. Increases in miR155 expression positively correlated with increasing maturity of monocyte and BMDC in both mouse and human microarrays, indicating its importance in development. We describe a requirement of miR155 for MHCII expression during GM-CSF-induced development and LPS-induced maturation of DCs, suggesting reduced immune function of DC when miR155 is absent. Our study suggests that miRNAs might have an important role in differentiation of myeloid cell such as dendritic cells and macrophages.

Up to now long-term in vitro growth of pro-B cells was thought to require stromal cells. However, here we show that fetal liver (FL) and bone marrow (BM) derived pro-B cells can be propagated long-term in stromal cell-free cultures supplemented with IL-7, stem cell factor and FLT3 ligand. Within a week, most cells expressed surface CD19, CD79A, λ5, and VpreB antigens and had rearranged immunoglobulin D-J heavy chain genes. Both FL and BM pro-B cells reconstituted the B-cell compartments of immuno-incompetent Rag2-deficient mice, with FL pro-B cells generating follicular, marginal zone (MZB) and B1a B cells, and BM pro-B cells giving rise mainly to MZB cells. Reconstituted Rag2-deficient mice generated significant levels of IgM and IgG antibodies to a type II T-independent antigen; mice reconstituted with FL pro-B cells generated surprisingly high IgG 1 titers. Finally, we show for the first time that mice reconstituted with mixtures of pro-B and pro-T cells propagated in stromal cell-free in vitro cultures mounted a T-cell-dependent antibody response. This novel stromal cell-free culture system facilitates our understanding of B-cell development and might be applied clinically., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Phospholipase D (PLD) and its product phosphatidic acid (PA) are emerging as essential regulators of cytoskeleton organization in plants. However, the underlying molecular mechanisms of PA-mediated microtubule reorganization in plants remain largely unknown. In this study, we used pharmacological and genetic approaches to analyze the function of Arabidopsis thaliana PLDα1 in the regulation of microtubule organization and cell development in response to microtubule-affecting drugs. Treatment with the microtubule-stabilizing drug paclitaxel resulted in less growth inhibition and decreased rightward slant of roots, longitudinal alignment of microtubules, and enhanced length of hypocotyl epidermal cells in the pldα1 mutant, the phenotype of which was rescued by exogenous application of PA. Moreover, the pldα1 mutant was sensitive to the microtubule-disrupting drugs oryzalin and propyzamide in terms of seedling survival ratio, left-skewing angle of roots and microtubule organization. In addition, both disruption and stabilization of microtubules induced by drugs activated PLDα1 activity. Our findings demonstrate that in A. thaliana, PLDα1/PA might regulate cell development by modulating microtubule organization in an activity-dependent manner.

The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein. In this article, we draw attention to the role of TCTP in cancer, especially, focusing on cell differentiation and tumor reversion, a biological process by which highly tumorigenic cells lose their malignant phenotype. This protein has been shown to be the most strongly downregulated protein in revertant cells compared to the parental cancer cells. Decreased expression of TCTP results either in the reprogramming of cancer cells into reversion or apoptosis. As conventional chemotherapy is frequently associated with the development of drug resistance and high toxicity, the urge for the development of new or additional scientific approaches falls into place. Differentiation therapy aims at reinducing differentiation backward to the nonmalignant cellular state. Here, different approaches have been reported such as the induction of retinoid pathways and the use of histone deacetylase inhibitors. Also, PPARγ agonists and the activation of the vitamin D receptor have been reported as potential targets in differentiation therapy. As TCTP is known as the histamine-releasing factor, antihistaminic drugs have been shown to target this protein. Antihistaminic compounds, hydroxyzine and promethazine, inhibited cell growth of cancer cells and decreased TCTP expression of breast cancer and leukemia cells. Recently, we found that two antihistaminics, levomepromazine and buclizine, inhibited cancer cell growth by direct binding to TCTP and induction of cell differentiation. These data confirmed that TCTP is an exquisite target for anticancer differentiation therapy and antihistaminics have potential to be lead compounds for the direct interaction with TCTP as new inhibitors of human TCTP and tumor growth.

Long non-coding RNAs (lncRNAs) have been attracting immense research interests. The relevance of lncRNAs in biological and physiological as well as in pathological processes has increased along with the understanding of their various regulatory mechanisms. Abundant studies have indicated that lncRNAs are involved in the differentiation, proliferation, activation, and initiation of apoptosis in different cell types. However, most studies about the regulating biology of lncRNAs are currently focused on cancer cells. This review is focused on the widely unexplored role of lncRNAs in the cell fate of myeloid cells. In this review, we summarize recent studies that have confirmed lncRNAs to be essential in the development of myeloid cells under normal and pathological conditions.

In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same.

Haematopoiesis is a process that is responsible for generating sufficient numbers of blood cells in the circulation and in tissues. It is central to maintenance of homeostasis within an animal, and is critical for defense against infection. While haematopoiesis is common to all animals possessing a circulatory system, the specific mechanisms and ultimate products of haematopoietic events vary greatly. Our understanding of this process in non-vertebrate organisms is primarily derived from those species that serve as developmental and immunological models, with sparse investigations having been carried out in other organisms spanning the metazoa. As research into the regulation of immune and blood cell development advances, we have begun to gain insight into haematopoietic events in a wider array of animals, including the molluscs. What began in the early 1900's as observational studies on the morphological characteristics of circulating immune cells has now advanced to mechanistic investigations of the cytokines, growth factors, receptors, signalling pathways, and patterns of gene expression that regulate molluscan haemocyte development. Emerging is a picture of an incredible diversity of developmental processes and outcomes that parallels the biological diversity observed within the different classes of the phylum Mollusca. However, our understanding of haematopoiesis in molluscs stems primarily from the three most-studied classes, the Gastropoda, Cephalopoda and Bivalvia. While these represent perhaps the molluscs of greatest economic and medical importance, the fact that our information is limited to only 3 of the 9 extant classes in the phylum highlights the need for further investigation in this area. In this review, we summarize the existing literature that defines haematopoiesis and its products in gastropods, cephalopods and bivalves., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

IL-34 and colony-stimulating factor 1 (CSF1) are two alternative ligands for the CSF1 receptor that play nonredundant roles in the development, survival, and function of tissue macrophages and Langerhans cells (LCs). In this study, we investigated the spatio-temporal production of IL-34 and its impact on skin LCs in the developing embryo and adult mice in the steady state and during inflammation using Il34(LacZ) reporter mice and newly generated inducible Il34-knockout mice. We found that IL-34 is produced in the developing skin epidermis of the embryo, where it promotes the final differentiation of LC precursors. In adult life, LCs required IL-34 to continually self-renew in the steady state. However, during UV-induced skin damage, LC regeneration depended on neutrophils infiltrating the skin, which produced large amounts of CSF1. We conclude that LCs require IL-34 when residing in fully differentiated and anatomically intact skin epidermis, but rely on neutrophil-derived CSF1 during inflammation. Our demonstration that neutrophils are an important source of CSF1 during skin inflammation may exemplify a mechanism through which neutrophils promote their subsequent replacement with mononuclear phagocytes., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Soft graphene nanofibers with recoverable electrical conductivity and excellent physicochemical stability are prepared by a controlled assembly technique. By using the soft graphene nanofibers for cellular electrical stimulation, the common inhibitory effect of long-term electrical stimulation on nerve growth and development is avoided, which usually happens with traditional 2D conductive materials., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

MicroRNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Aberrant expression of miRNAs is an important factor in the development and progression of disease. The canonical myomiRs (miR-1, -133 and -206) are central to the development and health of mammalian skeletal and cardiac muscles, but new findings show they have regulatory roles in the development of other mammalian non-muscle tissues, including nerve, brain structures, adipose and some specialised immunological cells. Moreover, the deregulation of myomiR expression is associated with a variety of different cancers, where typically they have tumor suppressor functions, although examples of an oncogenic role illustrate their diverse function in different cell environments. This review examines the involvement of the related myomiRs at the crossroads between cell development/tissue regeneration/tissue inflammation responses, and cancer development.

Background and Aims: Plant stature and shape are largely determined by cell elongation, a process that is strongly controlled at the level of the cell wall. This is associated with the presence of many cell wall proteins implicated in the elongation process. Several proteins and enzyme families have been suggested to be involved in the controlled weakening of the cell wall, and these include xyloglucan endotransglucosylases/hydrolases (XTHs), yieldins, lipid transfer proteins and expansins. Although expansins have been the subject of much research, the role and involvement of expansin-like genes/proteins remain mostly unclear. This study investigates the expression and function of AtEXLA2 (At4g38400), a member of the expansin-like A (EXLA) family in arabidposis, and considers its possible role in cell wall metabolism and growth., Methods: Transgenic plants of Arabidopsis thaliana were grown, and lines over-expressing AtEXLA2 were identified. Plants were grown in the dark, on media containing growth hormones or precursors, or were gravistimulated. Hypocotyls were studied using transmission electron microscopy and extensiometry. Histochemical GUS (β-glucuronidase) stainings were performed., Key Results: AtEXLA2 is one of the three EXLA members in arabidopsis. The protein lacks the typical domain responsible for expansin activity, but contains a presumed cellulose-interacting domain. Using promoter::GUS lines, the expression of AtEXLA2 was seen in germinating seedlings, hypocotyls, lateral root cap cells, columella cells and the central cylinder basally to the elongation zone of the root, and during different stages of lateral root development. Furthermore, promoter activity was detected in petioles, veins of leaves and filaments, and also in the peduncle of the flowers and in a zone just beneath the papillae. Over-expression of AtEXLA2 resulted in an increase of >10 % in the length of dark-grown hypocotyls and in slightly thicker walls in non-rapidly elongating etiolated hypocotyl cells. Biomechanical analysis by creep tests showed that AtEXLA2 over-expression may decrease the wall strength in arabidopsis hypocotyls., Conclusions: It is concluded that AtEXLA2 may function as a positive regulator of cell elongation in the dark-grown hypocotyl of arabidopsis by possible interference with cellulose metabolism, deposition or its organization., (© The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background and Aims: A key challenge in biology is to systematically investigate and integrate the different levels of information available at the global and single-cell level. Recent studies have elucidated spatiotemporal expression patterns of root cell types in Arabidopsis thaliana, and genome-wide quantification of polysome-associated mRNA levels, i.e. the translatome, has also been obtained for corresponding cell types. Translational control has been increasingly recognized as an important regulatory step in protein synthesis. The aim of this study was to investigate coupled transcription and translation by use of publicly available root datasets., Methods: Using cell-type-specific datasets of the root transcriptome and translatome of arabidopsis, a systematic assessment was made of the degree of co-ordination and divergence between these two levels of cellular organization. The computational analysis considered correlation and variation of expression across cell types at both system levels, and also provided insights into the degree of co-regulatory relationships that are preserved between the two processes., Key Results: The overall correlation of expression and translation levels of genes resemble an almost bimodal distribution (mean/median value of 0·08/0·12), with a second, less strongly pronounced 'mode' for negative Pearson's correlation coefficient values. The analysis conducted also confirms that previously identified key transcriptional activators of secondary cell wall development display highly conserved patterns of transcription and translation across the investigated cell types. Moreover, the biological processes that display conserved and divergent patterns based on the cell-type-specific expression and translation levels were identified., Conclusions: In agreement with previous studies in animal cells, a large degree of uncoupling was found between the transcriptome and translatome. However, components and processes were also identified that are under co-ordinated transcriptional and translational control in plant root cells., (© The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Background Aims: As we approach the era of mesenchymal stem cell (MSC) application in the medical clinic, the standarization of their culture conditions are of the particular importance. We re-evaluated the influences of oxygens concentration on proliferation, stemness and differentiation of human umbilical cord Wharton Jelly-derived MSCs (WJ-MSCs)., Methods: Primary cultures growing in 21% oxygen were either transferred into 5% O2 or continued to grow under standard 21% oxygen conditions. Cell expansion was estimated by WST1/enzyme-linked immunosorbent assay or cell counting. After 2 or 4 weeks of culture, cell phenotypes were evaluated using microscopic, immunocytochemical, fluorescence-activated cell-sorting and molecular methods. Genes and proteins typical of mesenchymal cells, committed neural cells or more primitive stem/progenitors (Oct4A, Nanog, Rex1, Sox2) and hypoxia inducible factor (HIF)-1α-3α were evaluated., Results: Lowering O2 concentration from 21% to the physiologically relevant 5% level substantially affected cell characteristics, with induction of stemness-related-transcription-factor and stimulation of cell proliferative capacity, with increased colony-forming unit fibroblasts (CFU-F) centers exerting OCT4A, NANOG and HIF-1α and HIF-2α immunoreactivity. Moreover, the spontaneous and time-dependent ability of WJ-MSCs to differentiate into neural lineage under 21% O2 culture was blocked in the reduced oxygen condition. Importantly, treatment with trichostatin A (TSA, a histone deacetylase inhibitor) suppressed HIF-1α and HIF-2α expression, in addition to blockading the cellular effects of reduced oxygen concentration., Conclusions: A physiologically relevant microenvironment of 5% O2 rejuvenates WJ-MSC culture toward less-differentiated, more primitive and faster-growing phenotypes with involvement of HIF-1α and HIF-2α-mediated and TSA-sensitive chromatin modification mechanisms. These observations add to the understanding of MSC responses to defined culture conditions, which is the most critical issue for adult stem cells translational applications., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)