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Abstract Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.

Genetically engineered macrophages (GEMs) have emerged as an appealing strategy to treat cancers, but they are largely impeded by the cell availability and technical challenges in gene transfer. Here, we develop an efficient approach to generate large-scale macrophages from human induced pluripotent stem cells (hiPSCs). Starting with 1 T150 dish of 106 hiPSCs, more than 109 mature macrophages (iMacs) could be generated within 1 month. The generated iMacs exhibit typical macrophage properties such as phagocytosis and polarization. We then generate hiPSCs integrated with an IL-12 expression cassette in the AAVS1 locus to produce iMacs secreting IL-12, a strong proimmunity cytokine. hiPSC-derived iMacs_IL-12 prevent cytotoxic T cell exhaustion and activate T cells to kill different cancer cells. Furthermore, iMacs_IL-12 display strong antitumor effects in a T cell-dependent manner in subcutaneously or systemically xenografted mice of human lung cancer. Therefore, we provide an off-the-shelf strategy to produce large-scale GEMs for cancer therapy.

Glazed tiles are characteristic architectural ceramics traditionally used in ancient Chinese royal buildings. Studies on their chemical compositions have provided valuable information regarding their compositional classifications and the provenances of their raw materials. Existing studies have mainly focused on the Yuan dynasty (1271–1368 AD) or later. Research on earlier ages is limited because of a lack of samples. In this study, we used an energy-dispersive X-ray fluorescence spectrometer to analyze the chemical compositions of 18 glazed tiles unearthed from an imperial mausoleum (the Xinli site) from the Liao dynasty (969–982 AD). The glazes of the tiles had a SiO2–Al2O3–PbO ternary oxidic system and the bodies of the tiles had a SiO2–Al2O3 binary oxidic system. Certain compositional differences were observed among the samples with different types of decorations. Compared with samples from the Yuan dynasty and later periods, the Xinli samples had higher SiO2 and Al2O3 contents and lower PbO and CuO contents in the tile glazes. The tile bodies of the Xinli samples had compositions similar to those of tile bodies from the Qing dynasty (1616–1912 AD). We speculated that the Xinli samples with different decorations came from different kiln sites.

Abstract Metastable ε-Fe2O3 was discovered on a ceramic ware of Deqing kiln of the Tang Dynasty, which coexists with α-Fe2O3 in the brown area between adjacent black glaze areas, and it is the earliest known artificially synthesized ε-Fe2O3. Based on the composition analysis of α-Fe2O3, ε-Fe2O3 and the glass phase around them, it is speculated that some Fe3+ ions were replaced by Al3+ ions during the formation of ε-Fe2O3, and a relatively low CaO content may be required for its crystallization. This work may promote researchers' understanding of ε-Fe2O3 crystals, and provide clues for the artificial synthesis of large ε-Fe2O3 crystals.

Abstract The hare’s fur glazed Jian wares characterized by radial fur-like strips, as one of the typical representatives of Chinese ceramics in the 10th-13th century (A.D.), were famous for the aesthetic values in highlighting the color sparkling effects of tea soup, which were one of the indispensable tea wares in tea culture. The firing technology of hare’s fur glaze of Jian wares not only played a crucial role in the development of Chinese ceramic history, but also enlightened the modern imitation technology. The hare’s fur glaze of Jian wares can be further grouped according to the color of strips, of which the yellowish-brown hare’s fur glaze (yellowish-brown matte strips), gold hare’s fur glaze (golden shiny strips) and silver hare’s fur glaze (bright silvery strips) were the most representative types. Epsilon-Fe2O3, a specific metastable crystal phase, has become a research hotspot as the chromogenic crystals of hare’s fur glaze, however, the comparative analysis focused on the correlation between ε-Fe2O3 and the macroscopic glaze color has been barely reported. In our work, the bright color strips (hare’s fur area) and black strips (black glaze area) of silver, gold and yellowish-brown hare’s fur glaze were morphologically and compositionally analyzed by SEM and EDS, respectively. The morphological features and compositional differences of three representative types of hare’s fur glaze samples were summarized, which indicated the differences in the size, distribution and coverage of crystals and the distribution and contents of materials. It was speculated that high-level of Fe2O3 and CaO with low-level of SiO2 and Al2O3 may relate to the crystallization of ε-Fe2O3. This work helps in laying the foundation of further explanation of the technological differences of hare’s fur glazes.

GFI1 is a DNA binding transcriptional repressor, it is shown to be an important gene associated with blood cells development and many blood diseases (Möröy et al., 2015). But the role of GFI1 in human hematopoietic development has not been known (Thambyrajah et al., 2016). To illustrate the function of GFI1 in human hematopoietic development, we constructed a GFI1-2 × flag-tag knock-in human embryonic stem cell line by CRISPR/Cas9 mediated gene targeting, and it would be the effective tool to study GFI1. The cell line could express GFI1-2 × flag-tag and can be identified with western blot and immunofluorescence. This cell line maintains stem cell morphology, and displays normal karyotype, pluripotent stem cell marker expression and differentiation potential.

Exosomes are lipid membrane bilayer-encapsulated vesicles secreted by cells into the extracellular space. They carry abundant inclusions (such as nucleic acids, proteins, and lipids) that play pivotal roles in intercellular communication. Tumor stem cells are capable of self-renewal and are crucial for survival, proliferation, drug resistance, metastasis, and recurrence of tumors. The miRNAs (microRNAs) in exosomes have various functions, such as participating in inflammatory response, cell migration, proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition. Tumor stem cells secrete exosomes that act as important messengers involved in various tumor processes and several studies provide increasing evidence supporting the importance of these exosomes in tumor recurrence and metastasis. This review primarily focuses on the production and secretion of exosomes from tumors and tumor stem cells and their effects on cancer progression. Cancer stem cancer derived exosome play an important massager in the tumor microenvironment. It also emphasizes on the study of tumor stem cell exosomes in the light of cancer metastasis and recurrence aiming to provide valuable insights and novel perspectives, which could be beneficial for developing effective diagnostic and treatment strategies.

Human MCPH1 (Microcephalin 1) encodes a DNA damage response protein. Mutations in this gene have been associated with Primary Autosomal Recessive Microcephaly and premature chromosome condensation syndrome. To further understand the roles of MCPH1 in neural differentiation and brain development, here we generated a MCPH1 knockout human embryonic stem cell line by CRISPR/Cas9 genome editing technology. This cell line maintained a normal karyotype and typical undifferentiated state in terms of morphology, pluripotent gene expression, and had differentiation potential in vitro. This cell line provides a good resource to study the role of MCPH1 gene in neurogenesis and regulation of the size of the cerebral cortex in vitro.

Conventional human pluripotent stem cells (hPSCs) fail to contribute to interspecies chimaeras when injected into mouse blastocysts. Here the authors show that forced expression of BMI1 overcomes apoptosis of hPSCs in blastocysts of mouse, rabbit and pig allowing them to contribute to chimaeras.

Abstract Tie luo (affixed hanging) was an expressive form of traditional Chinese calligraphy or paintings, and popular in the imperial palaces for interior decorations in Qing Dynasty (1644–1911 C.E.). A piece of calligraphic tie luo, written by an eminent calligrapher Gu Gao (1763–1832 C.E.), was restored recently in the Palace Museum, Beijing, China. The paper with pigment coating specially made for this calligraphic piece was named as fenjian. This article presented results from materials identification prior to the restoration. Multianalysis with scientific approaches revealed how tie luo was manufactured. It could be concluded that the investigated tie luo used a paper made from bast fibers of mulberry trees. And the decorative ground layer for the piece was also studied, which indicated that a type of organic red pigments were used for the masterpiece. White lead was considered as the main pigment, mixed with a red dye extracted from sappanwood. Meanwhile, animal glue, drying oils and beeswax were confirmed as the organic binding media. In dye analysis, protosappanin B and brazilin as well as brazilein were identified, which implied that sappanwood was used for the organic manufacture of pigments. In addition, both Nowik type A and C were found in the research, which were characteristic of sappanwood for identification.

Nesprins (nuclear envelope spectrin repeat proteins) are multi-isomeric scaffolding proteins. Giant nesprin-1 and -2 localise to the outer nuclear membrane, interact with SUN (Sad1p/ UNC-84) domain-containing proteins at the inner nuclear membrane to form the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex, which, in association with lamin A/C and emerin, mechanically couples the nucleus to the cytoskeleton. Despite ubiquitous expression of nesprin giant isoforms, pathogenic mutations in nesprin-1 and -2 are associated with tissue-specific disorders, particularly related to striated muscle such as dilated cardiomyopathy and Emery–Dreifuss muscular dystrophy. Recent evidence suggests this muscle-specificity might be attributable in part, to the small muscle specific isoform, nesprin-1α2, which has a novel role in striated muscle function. Our current understanding of muscle-specific functions of nesprin-1 and its isoforms will be summarised in this review to provide insight into potential pathological mechanisms of nesprin-related muscle disease and may inform potential targets of therapeutic modulation. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cells (HSCs)/progenitor cells (HPCs) are generated from hemogenic endothelial cells (HECs) during the endothelial-to-hematopoietic transition (EHT); however, the underlying mechanism remains poorly understood. Here, using an array of approaches, including CRSPR/Cas9 gene knockouts, RNA-Seq, ChIP-Seq, ATAC-Seq etc., we report that vitamin C (Vc) is essential in HPC generation during human pluripotent stem cell (hPSC) differentiation in defined culture conditions. Mechanistically, we found that the endothelial cells generated in the absence of Vc fail to undergo the EHT because of an apparent failure in opening up genomic loci essential for hematopoiesis. Under Vc deficiency, these loci exhibited abnormal accumulation of histone H3 trimethylation at Lys-27 (H3K27me3), a repressive histone modification that arose because of lower activities of demethylases that target H3K27me3. Consistently, deletion of the two H3K27me3 demethylases, Jumonji domaincontaining 3 (JMJD3 or KDM6B) and histone demethylase UTX (UTX or KDM6A), impaired HPC generation even in the presence of Vc. Furthermore, we noted that Vc and jmjd3 are also important for HSC generation during zebrafish development. Together, our findings reveal an essential role for Vc in the EHT for hematopoiesis, and identify KDM6-mediated chromatin demethylation as an important regulatory mechanism in hematopoietic cell differentiation. [ABSTRACT FROM AUTHOR]