Single cell RNA sequencing of cultured endometrial mesenchymal stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE149651 | GEO | 2021/06/01
REPOSITORIES: GEO
Similar Datasets
Project description:A population of endometrial cells displaying key properties of mesenchymal stem cells (eMSC) has been identified in human endometrium. eMSC co-express CD146 and PDGFRB surface markers, have a perivascular location, and likely represent the reservoir of progenitors giving rise to the endometrial stromal fibroblast lineage. Endometrial stromal cells isolated from 16 oocyte donors and 3 benign gynecologic surgery subjects were FACS sorted into four populations: CD146+/PDGFRB+ (eMSC); CD146+/PDGFRB- (endothelial cells); CD146-/PDGFRB+ (stromal fibroblasts); CD146-/PDGFRB- (mixed population) then subjected to gene expression analysis on Affymetrix Human Gene 1.0 ST arrays, and differentially expressed genes compared between eMSC, stromal fibroblast, and endothelial cell populations. Ninety-two genes were validated by multiplex quantitative RT-PCR on seventy of these sorted cell populations. Immunohistochemistry was used to verify the perivascular location of eMSCs.Principal component analysis and hierarchical clustering showed eMSC clustering discretely near stromal fibroblasts and separately from endothelial cells. eMSC expressed pericyte markers and genes involved hypoxia response, inflammation, proteolysis, and angiogenesis/vasculogenesis – all relevant to endometrial tissue breakdown and regeneration. Additionally, eMSC displayed distinct gene profiles for cell-cell communication and regulation of gene expression. Overall, the phenotype of the eMSC is that of a multipotent pericyte responsive to hypoxic, proteolytic, and inflammatory stimuli, able to induce angiogenesis, migrate and differentiate into lineage cells, and potentially respond to estradiol and progesterone. Identifying the pathways and gene families described herein in the context of the endometrial niche, will be valuable in understanding normal and abnormal endometrial development in utero and differentiation in adult uterus. The multipotent, perivascular endometrial mesenchymal stem cell has a “niche phenotype” of high Notch, TGFB, IGF, and Hedgehog and low canonical/non-canonical Wnt and EGF signaling. Oocyte donors with no known uterine pathology underwent endometrial biopsy at the time of oocyte retrieval, following comparable GnHR agonist downregulated ovarian stimulation protocols. Tissue was digested and stromal cells isolated and sorted based on expression of CD146 and PDGFRB. RNA was extracted and hybridized on Affymetrix microarrays. Resulting data were compared between sorted isolated cell populations.
2011-11-14 | E-GEOD-31152 | biostudies-arrayexpress
Project description:A population of endometrial cells displaying key properties of mesenchymal stem cells (eMSC) has been identified in human endometrium. eMSC co-express CD146 and PDGFRB surface markers, have a perivascular location, and likely represent the reservoir of progenitors giving rise to the endometrial stromal fibroblast lineage. Endometrial stromal cells isolated from 16 oocyte donors and 3 benign gynecologic surgery subjects were FACS sorted into four populations: CD146+/PDGFRB+ (eMSC); CD146+/PDGFRB- (endothelial cells); CD146-/PDGFRB+ (stromal fibroblasts); CD146-/PDGFRB- (mixed population) then subjected to gene expression analysis on Affymetrix Human Gene 1.0 ST arrays, and differentially expressed genes compared between eMSC, stromal fibroblast, and endothelial cell populations. Ninety-two genes were validated by multiplex quantitative RT-PCR on seventy of these sorted cell populations. Immunohistochemistry was used to verify the perivascular location of eMSCs.Principal component analysis and hierarchical clustering showed eMSC clustering discretely near stromal fibroblasts and separately from endothelial cells. eMSC expressed pericyte markers and genes involved hypoxia response, inflammation, proteolysis, and angiogenesis/vasculogenesis – all relevant to endometrial tissue breakdown and regeneration. Additionally, eMSC displayed distinct gene profiles for cell-cell communication and regulation of gene expression. Overall, the phenotype of the eMSC is that of a multipotent pericyte responsive to hypoxic, proteolytic, and inflammatory stimuli, able to induce angiogenesis, migrate and differentiate into lineage cells, and potentially respond to estradiol and progesterone. Identifying the pathways and gene families described herein in the context of the endometrial niche, will be valuable in understanding normal and abnormal endometrial development in utero and differentiation in adult uterus. The multipotent, perivascular endometrial mesenchymal stem cell has a “niche phenotype” of high Notch, TGFB, IGF, and Hedgehog and low canonical/non-canonical Wnt and EGF signaling.
2011-11-14 | GSE31152 | GEO
Project description:The study profiles endometrial samples from donors in reproductive age with and without endometriosis collected during natural cycles. Samples where profiled with Visium Spatial transcriptomics using 10x technology (v1 3').
2024-05-13 | E-MTAB-14058 | biostudies-arrayexpress
Project description:Diabetic retinopathy (DR) is the leading cause of blindness in working-age people. Pericyte loss is one of the pathologic cellular events in DR, which weakens the retinal microvessels. Damages to the microvascular networks are irreversible and permanent, thus further progression of DR is inevitable. In this study, we hypothesize that multipotent perivascular progenitor cells derived from human ESCs (hESC-PVPCs) improve the damaged retinal vasculature in the streptozotocin (STZ)-induced diabetic rodent models. We describe a highly efficient and feasible protocol to derive such cells using a natural selection method without cell sorting processes. As a cellular model of pericytes, hESC-PVPCs exhibited marker expressions such as CD140B, CD146, NG2, and functional characteristics of pericytes. Following a single intravitreal injection into diabetic Brown Norway (BN) rats, we demonstrate that the cells localized alongside typical perivascular regions of the retinal vasculature, and stabilized blood-retinal barrier (BRB) breakdown. Findings in this study highlight a therapeutic potential of hESC-PVPCs in DR by mimicking the role of pericytes in vascular stabilization.
2016-01-22 | GSE77114 | GEO
Project description:The endometrial perivascular microenvironment is rich in mesenchymal stem-like cells that express type 1 integral membrane protein Sushi domain containing 2 (SUSD2) but the role of these cells in the decidual transformation of this tissue in pregnancy is unknown. We used an antibody directed against SUSD2 (W5C5) to isolate perivascular (W5C5+) and non-perivascular (W5C5-) fibroblasts from mid-luteal biopsies. We show that SUSD2 expression, and hence the ratio of W5C5+ to W5C5- cells, changes in culture depending on cell-cell contact and activation of the Notch signaling pathway. RNA sequencing revealed that cultures derived from W5C5+ progenitor cells remain phenotypically distinct by the enrichment of novel and established endometrial perivascular signature genes. In an undifferentiated state, W5C5+-derived cells produced lower levels of various chemokines and inflammatory modulators when compared to their W5C5- counterparts. This divergence in secretomes became more pronounced upon decidualization, which transformed perivascular W5C5+ cells into the dominant source of a range of trophic and immunomodulatory cytokines, including leukemia inhibitory factor (LIF). Our findings indicate that the decidual response is spatially organized with differentiating perivascular cells establishing distinct cytokine and chemokine gradients that could direct trophoblast towards maternal vessels and govern local immune responses in pregnancy. Analysis of paired human endometrial stromal cultures, originating from either W5C5+ or W5C5- cells, from four biological replicates - a total of 8 samples - by Illumina RNAseq.
2014-10-29 | E-GEOD-57182 | biostudies-arrayexpress
Project description:The human endometrium is a highly heterogeneous tissue comprising multiple cell-types and cellular states that change in cycle-dependent manner. This tissue heterogeneity is a major drawback when interpreting bulk (whole biopsy) transcriptomic data. To address this hurdle, RNA-seq analysis was performed on four isolated stromal cell populations [SUSD2+ perivascular stromal cells (PVCs), endometrial stromal cells (EnSCs), SUSD2+ clonal cells (MSCs), and clonal transit amplifying cells (TAs)], glandular epithelial cells, uNK cells, and matched whole tissue. Transcriptomic data were obtained for 3 whole endometrial biopsies and 6 matched, purified cell populations.
2020-10-09 | GSE159266 | GEO
Project description:Various mesenchymal cell types have been identified as critical components of the hematopoietic stem/progenitor cell (HSPC) niche. Although several groups have described the generation of mesenchyme from human pluripotent stem cells (hPSC), the capacity of such cells to support hematopoiesis has not been reported. Here we have demonstrated that distinct mesenchymal subpopulations co-emerge from mesoderm during hPSC differentiation. Despite co-expression of common mesenchymal markers (CD73, CD105, CD90, PDGFRβ), a subset of cells defined as CD146++CD140alow supported functional HSPC ex vivo while CD146-CD140a+ cells drove differentiation. The CD146++ subset expressed genes associated with the HSPC niche and high levels of the Wnt inhibitors. HSPC support was contact-dependent and was mediated in part through JAG1 expression. Molecular profiling revealed remarkable transcriptional similarity between hPSC-derived CD146++ and primary human CD146++ perivascular cells. The derivation of diverse pools of mesenchymal populations from hPSC opens potential avenues to model their developmental and functional differences and to improve cell-based therapeutics from hPSC.
2018-03-07 | GSE83443 | GEO
Project description:Single cell RNA sequencing of cultured endometrial mesenchymal stem cells
| PRJNA629541 | ENA
Project description:Mesenchymal stromal cells (MSCs) are cultured cells that can give rise to mature mesenchymal cells under appropriate conditions, and secrete a number of biologically relevant molecules that may play an important role in regenerative medicine. Evidence indicates that pericytes (PCs) correspond to mesenchymal stem cells in vivo and can give rise to MSCs when cultured, but a comparison between the gene expression profiles of cultured PCs (cPCs) and MSCs is lacking. We have devised a novel methodology to isolate PCs from human adipose tissue, and compared cPCs to MSCs obtained through traditional methods. Freshly isolated PCs expressed CD34, CD140b, and CD271 on their surface, but not CD146. Both MSCs and cPCs were able to differentiate along mesenchymal pathways in vitro, displayed an essentially identical surface immunophenotype, and exhibited the ability to suppress CD3+ lymphocyte proliferation in vitro. Microarray expression data of cPCs and MSCs formed a single cluster among other cell types. Further analyses showed that the gene expression profiles of cPCs and MSCs are extremely similar, although MSCs differentially expressed endothelial cell-specific transcripts. These results confirm, using the power of transcriptomic analysis, that PCs give rise to MSCs, and suggest that low levels of endothelial cells may persist in MSC cultures established using traditional protocols.
2015-07-22 | GSE67747 | GEO
Project description:The identification of target genes at genome-wide association study (GWAS) loci is a major obstacle for GWAS follow-up. To identify candidate target genes at the 16 known endometrial cancer GWAS risk loci, we performed HiChIP chromatin looping analysis of endometrial cell lines. To enrich for enhancer-promoter interactions, a mechanism through which GWAS variation may target genes, we captured loops associated with H3K27Ac histone, characteristic of promoters and enhancers. Analysis of HiChIP loops contacting promoters revealed enrichment for endometrial cancer GWAS heritability and intersection with endometrial cancer risk variation identified 103 HiChIP target genes at 13 risk loci. Expression of four HiChIP target genes (SNX11, SRP14, HOXB2 and BCL11A) was associated with risk variation, providing further evidence for their regulation. Network analysis functionally prioritized a set of proteins that interact with those encoded by HiChIP target genes, and this set was enriched for pan-cancer and endometrial cancer drivers. Lastly, HiChIP target genes and prioritized interacting proteins were over-represented in pathways related to endometrial cancer development. In summary, we have generated the first global chromatin looping data from endometrial cells, enabling analysis of all known endometrial cancer risk loci and identifying biologically relevant candidate target genes.
2020-04-13 | GSE137936 | GEO