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Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells

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 (hPSCs), the capacity of such cells to support hematopoiesis has no...

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Autores principales: Chin, Chee Jia, Li, Suwen, Corselli, Mirko, Casero, David, Zhu, Yuhua, He, Chong Bin, Hardy, Reef, Péault, Bruno, Crooks, Gay M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830911/
https://www.ncbi.nlm.nih.gov/pubmed/29307583
http://dx.doi.org/10.1016/j.stemcr.2017.12.005
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author Chin, Chee Jia
Li, Suwen
Corselli, Mirko
Casero, David
Zhu, Yuhua
He, Chong Bin
Hardy, Reef
Péault, Bruno
Crooks, Gay M.
author_facet Chin, Chee Jia
Li, Suwen
Corselli, Mirko
Casero, David
Zhu, Yuhua
He, Chong Bin
Hardy, Reef
Péault, Bruno
Crooks, Gay M.
author_sort Chin, Chee Jia
collection PubMed
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 (hPSCs), the capacity of such cells to support hematopoiesis has not been reported. Here, we demonstrate that distinct mesenchymal subpopulations co-emerge from mesoderm during hPSC differentiation. Despite co-expression of common mesenchymal markers (CD73, CD105, CD90, and PDGFRβ), a subset of cells defined as CD146(hi)CD73(hi) expressed genes associated with the HSPC niche and supported the maintenance of functional HSPCs ex vivo, while CD146(lo)CD73(lo) cells supported differentiation. Stromal support of HSPCs was contact dependent and mediated in part through high JAG1 expression and low WNT signaling. Molecular profiling revealed significant transcriptional similarity between hPSC-derived CD146(++) and primary human CD146(++) perivascular cells. The derivation of functionally diverse types of mesenchyme from hPSCs opens potential avenues to model the HSPC niche and develop PSC-based therapies.
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spelling pubmed-58309112018-03-06 Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells Chin, Chee Jia Li, Suwen Corselli, Mirko Casero, David Zhu, Yuhua He, Chong Bin Hardy, Reef Péault, Bruno Crooks, Gay M. Stem Cell Reports Article 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 (hPSCs), the capacity of such cells to support hematopoiesis has not been reported. Here, we demonstrate that distinct mesenchymal subpopulations co-emerge from mesoderm during hPSC differentiation. Despite co-expression of common mesenchymal markers (CD73, CD105, CD90, and PDGFRβ), a subset of cells defined as CD146(hi)CD73(hi) expressed genes associated with the HSPC niche and supported the maintenance of functional HSPCs ex vivo, while CD146(lo)CD73(lo) cells supported differentiation. Stromal support of HSPCs was contact dependent and mediated in part through high JAG1 expression and low WNT signaling. Molecular profiling revealed significant transcriptional similarity between hPSC-derived CD146(++) and primary human CD146(++) perivascular cells. The derivation of functionally diverse types of mesenchyme from hPSCs opens potential avenues to model the HSPC niche and develop PSC-based therapies. Elsevier 2018-01-04 /pmc/articles/PMC5830911/ /pubmed/29307583 http://dx.doi.org/10.1016/j.stemcr.2017.12.005 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Chin, Chee Jia
Li, Suwen
Corselli, Mirko
Casero, David
Zhu, Yuhua
He, Chong Bin
Hardy, Reef
Péault, Bruno
Crooks, Gay M.
Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells
title Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells
title_full Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells
title_fullStr Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells
title_full_unstemmed Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells
title_short Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells
title_sort transcriptionally and functionally distinct mesenchymal subpopulations are generated from human pluripotent stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830911/
https://www.ncbi.nlm.nih.gov/pubmed/29307583
http://dx.doi.org/10.1016/j.stemcr.2017.12.005
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