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SRP076677
Homo sapiens
20 Downloadable Samples
Illumina HiSeq 2000
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, PDGFRß), 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. Overall design: Our goal was to analyze and compare transcriptome of human pluripoten stem cell-derived mesenchyme (CD146++ and CD146-) with primary human lipoaspirate tissue-derived pericyte (CD146+) and CD146- mesenchymal populations.
Publication Title
Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Although clonal studies of lineage potential have been extensively applied to organ specific stem and progenitor cells, much less is known about the clonal origins of lineages formed from the germ layers in early embryogenesis. We applied lentiviral tagging followed by vector integration site analysis (VISA) with high-throughput sequencing to investigate the ontogeny of the hematopoietic, endothelial and mesenchymal lineages as they emerge from human embryonic mesoderm. In contrast to studies that have used VISA to track differentiation of self-renewing stem cell clones that amplify significantly over time, we focused on a population of progenitor clones with limited self-renewal capability. Our analyses uncovered the critical influence of sampling on the interpretation of lentiviral tag sharing, particularly among complex populations with minimal clonal duplication. By applying a quantitative framework to estimate the degree of undersampling we revealed the existence of tripotent mesodermal progenitors derived from pluripotent stem cells, and the subsequent bifurcation of their differentiation into exclusively bipotent endothelial/hematopoietic or endothelial/mesenchymal progenitors. Overall design: Our goal was to analyze transcriptome changes of mesoderm commitment during human embyronic stem cells differentiation. RNA were extracted and sequenced from two populations, human embryonic stem cells (H1 line) and the human early mesodermal progenitors (hEMP) differentiated from H1.
Publication Title
Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells.
Sample Metadata Fields
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