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Additional file 1: File S1. List of physicochemical properties related to DPCP and TPCP. File S2. Name of the features and their mapping. File S3. Selected top features and their importance based on SHAP analysis for locations.

Poster by Ahmed K. Elsayed, Nehad M. Alajez, and Essam M. Abdelalim (Hamad Bin Khalifa University) Background: Our recent studies showed that FOXA2 plays a key role in the development of endocrine and exocrine pancreas. Downregulation of FOXA2 expression during differentiation of induced pluripotent stem cells (iPSCs) into pancreatic islets leads to a significant reduction in α-and β-cell masses. However, whether these changes are associated with alterations in the expression profile of the long non-coding RNAs (lncRNAs) remains unclear. Objective: the objective of this study is to investigate the alterations in the lncRNA profile and its relationship with the dysregulated mRNAs at the pancreatic progenitors (PPs) and pancreatic islet stages lacking FOXA2. Methods: Therefore, here, we used our recently established iPSCs lacking FOXA2 (FOXA2-/- iPSCs). we screened the dysregulated lncRNAs in the pancreatic progenitors (PPs) and β-cell stage derived from FOXA2-/- iPSCs in comparison to its control. Results: PPs and islet cells lacking FOXA2 showed several dysregulated lncRNAs in comparison to controls. Differential expression analysis identified 442 downregulated and 114 upregulated lncRNAs in PPs and 177 downregulated and 59 upregulated in the β-cell stage. Correlation analysis revealed 12 DE-lncRNAs, which were strongly correlated to key downregulated pancreatic genes in both pancreatic progenitors and beta cell stages (MEG3, H19, ZNF667-AS1, LINC00543, LINC00261, AC097639.1, AL035661.1, SLC25A25-AS1, U73166.1, ZNF790-AS1, MNX1-AS2, and AC091563.1). Conclusion: Our results showed a strong correlation of lncRNAs to several key pancreatic genes and TFs during pancreatic differentiation. Furthermore, these data suggest that the FOXA2-related defective pancreatic islet development is associated with significant alterations in the expression profile of lncRNAs.

Long non-coding RNAs (lncRNAs) represent a class of epigenetic regulators implicated in a number of physiological and pathological conditions. Herein, we characterized the lncRNA expression portrait from 837 patients with invasive breast cancer and 105 normals from the cancer genome atlas (TCGA), which revealed eighteen upregulated and forty-six downregulated lncRNAs. Clustering analysis revealed distinct lncRNA profile for the triple negative breast cancer (TNBC) and normal breast tissue, while less separation was observed among the HER2+HR+, HER2+HR−, HER2−HR+ molecular subtypes. LINC01614, and LINC01235 correlated with worse disease-free survival (DFS), while the expression of lnc-LRR1–1, lnc-ODF3B-2, AC015712.5, lnc-LAMB3–1, lnc-SPP2–3, and lnc-MAP9–2 correlated with better DFS. The expression of LINC01235 correlated with worse overall survival (OS), while the expression of MIR205HG, lnc-MAP2K6–5, FGF14-AS2, lnc-SPP2–3 correlated with better OS. Highest expression of LINC01614 was observed in progesterone receptor (PR)+, Estrogen receptor (PR)+, and HER2+ tumors, while lowest expression was in TNBC. Concordantly, LINC01614 was highly expressed in the luminalB/HER2+ subtype from the SRP062132 dataset. Elevated expression of LINC01614 was subsequently validated in primary breast cancer tissue and breast cancer cell lines. Bioinformatics and pathway analyses on LINC01614high vs. LINC01614low BC tissue revealed TGFβ1 and ECM as the most activated networks in LINC01614high tumors. Concordantly, strong correlation between the expression of LINC01614 and COL10A1 (R2 = 0.6929), SPOCK1 (R2 = 0.5156), ZEB1 (R2 = 0.3372), TGFBI (R2 = 0.2978), TGFB1 (R2 = 0.1985), ACTA2 (R2 = 0.1833), and TAGLN (R2 = 0.1909) was observed. Mechanistically, exogenous TGFB1 induced LINC01614 expression in the BT474 triple positive BC model, while small-molecule inhibition of transforming growth factor β (TGFβ, SB-431542) or focal adhesion kinase (FAK, PF-573228) abrogated LINC01614 expression. Our data revealed the lncRNA transcription landscape in breast cancer and its molecular subtypes. Our data provide novel insight implicating LINC01614 as unfavorable prognostic marker in BC, its association with the HR+/HER2+ BC molecular subtype and its regulation by TGFβ and FAK signaling.Other Information Published in: Cell Death Discovery License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41420-019-0190-6

COVID-19: complexity of disease severity revealed by systemic and localized single cell immune atlasOther Information Published in: Signal Transduction and Targeted Therapy License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41392-021-00587-3

Additional file 1: Figure S1. 5-mC-specific dot blot assay of gDNA of DNMT inhibitors treated TNBC models.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells with potent immunosuppressive functions, which can inhibit the activation of immune responses under a steady-state condition and pathological conditions. We performed transcriptomic profiling of circulating CD33+HLA-DR+ myeloid antigen-presenting cells (APCs) and CD33+HLA-DR– myeloid cells (potentially MDSCs) in healthy individuals. We sorted both subpopulations from peripheral blood mononuclear cells (PBMCs) of 10 healthy donors and performed RNA sequencing (RNA-Seq). We found that several signaling pathways associated with the positive regulation of immune responses, such as antigen presentation/processing, FcγR-mediated phagocytosis and immune cell trafficking, phosphoinositide 3-kinase (PI3K)/Akt signaling, DC maturation, triggering receptor expressed on myeloid cells 1 (TREM1) signaling, nuclear factor of activated T cells (NFAT) and IL-8 signaling were downregulated in CD33+HLA-DR– myeloid cells. In contrast, pathways implicated in tumor suppression and anti-inflammation, including peroxisome proliferator-activated receptor (PPAR) and phosphatase and tensin homolog (PTEN), were upregulated in CD33+HLA-DR– myeloid cells. These data indicate that PPAR/PTEN axis could be upregulated in myeloid cells to keep the immune system in check in normal physiological conditions. Our data reveal some of the molecular and functional differences between CD33+HLA-DR+ APCs and CD33+HLA-DR– myeloid cells in a steady-state condition, reflecting the potential suppressive function of CD33+HLA-DR– myeloid cells to maintain immune tolerance. For future studies, the same methodological approach could be applied to perform transcriptomic profiling of myeloid subsets in pathological conditions.

The interaction between cancer cells and molecular cues provided by tumor stromal cells plays a crucial role in cancer growth and progression. We have recently reported that the outcome of interaction between tumor cells and stromal cells is dependent on the gene expression signature of tumor cells. In the current study, we observed that several cancer cell lines, e.g., MCF7 breast cancer line, exhibited growth advantage when cultured in the presence of conditioned media (CM) derived from human bone marrow stromal stem cells (hBMSCs). Regarding the underlying molecular mechanism, we have identified CXCR7 as highly expressed by MCF7 cells and that it mediated the enhanced growth in response to hBMSC CM. Regarding the clinical relevance, we found an inverse correlation between the level of tumor gene expression of CXCR7 in bladder, breast, cervical, kidney, liver, lung, pancreatic, stomach, and uterine cancers, and patients’ overall survival. Interestingly, significant positive correlation between CXCR7 and CXCL12 gene expression (Pearson = 0.3, p = 2.0 × 10–16) was observed in breast cancer patients, suggesting a biological role for the CXCR7/CXCL12 genetic circuit in breast cancer biology. Our data provide insight into the molecular mechanisms by which stromal-derived microenvironmental cues mediate CXCR7 signaling and growth enhancement of breast cancer cells. Therapeutic targeting of this circuit might provide novel therapeutic opportunity for breast cancer.Other Information Published in: Cell Death Discovery License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41420-019-0169-3

ProblemStudying cancer tumors microenvironment may reveal a novel role in driving cancer progression and metastasis. The biological interaction between stromal (mesenchymal) stem cells (MSCs) and cancer cells remains incompletely understood. Herein, we investigated the effects of tumor cells’ secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs.BackgroundOver the past several years, significant amount of research has emerged documenting a role for MSCs in promoting epithelial-to-mesenchymal transition (ETM), and accelerating tumor growth and metastasis. In addition, MSCs are being introduced into therapy for a number of clinical indications and there is a concern of possible promoting effects on tumour growth by MSCs. On the other hand, several other studies reported that MSCs exert tumor suppressive effects. Therefore, understanding the crosstalk between MSCs and tumor growth is very crucial for the safe utilization of MSCs in regenerative medicineHypothesis Given this complex interplay between MSCs and tumor cells, the goal of this study was to assess the cellular and molecular changes in MSCs in response to secreted factors present in conditioned media (CM) from a panel of human tumor cell lines covering a spectrum of human cancers (Breast, Prostate, Lung, colon, and head and neck). ResearchMorphological changes were assessed using fluorescence microscopy. Changes in gene expression were assessed using Agilent microarray and qRT-PCR. GeneSpring X and DAVID tools were used for bioinformatic and signaling pathway analyses. Cell migration was assessed using transwell migration system. SB-431542, PF-573228, and PD98059 were used to inhibit TGFb, FAK, and MAPKK pathways, respectively. IL1b was measured using ELISA.ObservationsMSCs exposed to secreted factors present in conditioned media (CM) from FaDu, MDA-MB-231, PC-3, and NCI-H522, but not from MCF7 and HT-29, developed an elongated, spindle-shaped morphology with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK severely impaired the pro-inflammatory response of MSCs to tumor CM (~80-99%, and 55-88% inhibition, respectively), while inhibition of the TGFb pathway was found to promote the pro-inflammatory response (~3-fold increase). In addition, bioinformatics and pathway analysis of gene expression data from tumor cell lines combined with experimental validation revealed tumor-derived IL1b as one mediator of the pro-inflammatory phenotype observed in MSCs exposed to tumor CM. MSCs exhibited significant tropism toward secreted factors from the aforementioned tumor cell lines, while both normal and MSCs exposed to tumor conditioned media were capable of attracting human peripheral blood mononuclear cells (PBMCs). Conclusions: Our data revealed tumor-derived IL1b as one mediator of the pro-inflammatory response in MSCs exposed to tumor CM, which was found to be positively regulated by FAK and MAPK signaling, and negatively regulated by TGFb signaling. Thus, our data support a model where MSCs could promote cancer progression through becoming pro- inflammatory cells within the cancer stroma.