Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells
Summary: 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 hematopoies...
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Format: | Article |
Language: | English |
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Elsevier
2018-02-01
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Series: | Stem Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117305532 |
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author | Chee Jia Chin Suwen Li Mirko Corselli David Casero Yuhua Zhu Chong Bin He Reef Hardy Bruno Péault Gay M. Crooks |
author_facet | Chee Jia Chin Suwen Li Mirko Corselli David Casero Yuhua Zhu Chong Bin He Reef Hardy Bruno Péault Gay M. Crooks |
author_sort | Chee Jia Chin |
collection | DOAJ |
description | Summary: 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 CD146hiCD73hi expressed genes associated with the HSPC niche and supported the maintenance of functional HSPCs ex vivo, while CD146loCD73lo 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. : Crooks and colleagues demonstrated a previously underappreciated functional and molecular heterogeneity in mesenchyme generated from human pluripotent stem cells. Two mesenchymal subsets were distinguished by the reciprocal expression of CD146, CD73, and CD140a. CD146hiCD73hi mesenchyme supported self-renewing hematopoietic stem and progenitor cells (HSPCs), expressed markers of the HSPC niche, and shared a similar molecular signature with primary human adult pericytes. Keywords: pluripotent stem cell, mesenchyme, hematopoietic stem cell niche, pericyte biology, directed differentiation, mesoderm |
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format | Article |
id | doaj.art-ef2e4bbc77a14fbd97b01cc105b97f69 |
institution | Directory Open Access Journal |
issn | 2213-6711 |
language | English |
last_indexed | 2024-04-13T00:56:55Z |
publishDate | 2018-02-01 |
publisher | Elsevier |
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series | Stem Cell Reports |
spelling | doaj.art-ef2e4bbc77a14fbd97b01cc105b97f692022-12-22T03:09:38ZengElsevierStem Cell Reports2213-67112018-02-01102436446Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem CellsChee Jia Chin0Suwen Li1Mirko Corselli2David Casero3Yuhua Zhu4Chong Bin He5Reef Hardy6Bruno Péault7Gay M. Crooks8Department of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USADepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USABecton Dickinson, San Diego, CA 92121, USADepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USADepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USADepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USADepartment of Orthopedics, DGSOM, UCLA, Los Angeles, CA 90095, USA; Orthopedic Hospital Research Center, UCLA, Los Angeles, CA 90095, USA; Broad Stem Cell Research Center (BSCRC), UCLA, Los Angeles, CA 90095, USA; Department of Medicine, University of Indiana, Indianapolis, IN 46202, USADepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USA; Department of Orthopedics, DGSOM, UCLA, Los Angeles, CA 90095, USA; Orthopedic Hospital Research Center, UCLA, Los Angeles, CA 90095, USA; Broad Stem Cell Research Center (BSCRC), UCLA, Los Angeles, CA 90095, USA; Center for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UKDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USA; Broad Stem Cell Research Center (BSCRC), UCLA, Los Angeles, CA 90095, USA; Department of Pediatrics, DGSOM, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center (JCCC), UCLA, Los Angeles, CA 90095, USA; Corresponding authorSummary: 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 CD146hiCD73hi expressed genes associated with the HSPC niche and supported the maintenance of functional HSPCs ex vivo, while CD146loCD73lo 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. : Crooks and colleagues demonstrated a previously underappreciated functional and molecular heterogeneity in mesenchyme generated from human pluripotent stem cells. Two mesenchymal subsets were distinguished by the reciprocal expression of CD146, CD73, and CD140a. CD146hiCD73hi mesenchyme supported self-renewing hematopoietic stem and progenitor cells (HSPCs), expressed markers of the HSPC niche, and shared a similar molecular signature with primary human adult pericytes. Keywords: pluripotent stem cell, mesenchyme, hematopoietic stem cell niche, pericyte biology, directed differentiation, mesodermhttp://www.sciencedirect.com/science/article/pii/S2213671117305532 |
spellingShingle | Chee Jia Chin Suwen Li Mirko Corselli David Casero Yuhua Zhu Chong Bin He Reef Hardy Bruno Péault Gay M. Crooks Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells Stem Cell Reports |
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 |
url | http://www.sciencedirect.com/science/article/pii/S2213671117305532 |
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