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Stem Cell Reports. 2018 Feb 13;10(2):436-446. doi: 10.1016/j.stemcr.2017.12.005. Epub 2018 Jan 4.

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

Author information

1
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine (DGSOM), University of California (UCLA), Los Angeles, CA 90095, USA.
2
Becton Dickinson, San Diego, CA 92121, USA.
3
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; Department of Medicine, University of Indiana, Indianapolis, IN 46202, USA.
4
Department 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, UK.
5
Department 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. Electronic address: gcrooks@mednet.ucla.edu.

Abstract

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.

KEYWORDS:

directed differentiation; hematopoietic stem cell niche; mesenchyme; mesoderm; pericyte biology; pluripotent stem cell

PMID:
29307583
PMCID:
PMC5830911
DOI:
10.1016/j.stemcr.2017.12.005
[Indexed for MEDLINE]
Free PMC Article

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