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Cell Rep. 2017 May 30;19(9):1902-1916. doi: 10.1016/j.celrep.2017.05.019.

Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts.

Author information

1
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA.
2
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53703, USA.
3
Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
4
Department of Surgery, University of Wisconsin-Madison, Madison, WI 53792, USA.
5
Morgridge Institute for Research, Madison, WI 53707, USA.
6
Morgridge Institute for Research, Madison, WI 53707, USA; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53707, USA; Department of Molecular, Cellular & Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
7
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53707, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53792, USA. Electronic address: islukvin@wisc.edu.

Abstract

Elucidating the pathways that lead to vasculogenic cells, and being able to identify their progenitors and lineage-restricted cells, is critical to the establishment of human pluripotent stem cell (hPSC) models for vascular diseases and development of vascular therapies. Here, we find that mesoderm-derived pericytes (PCs) and smooth muscle cells (SMCs) originate from a clonal mesenchymal progenitor mesenchymoangioblast (MB). In clonogenic cultures, MBs differentiate into primitive PDGFRβ+CD271+CD73- mesenchymal progenitors, which give rise to proliferative PCs, SMCs, and mesenchymal stem/stromal cells. MB-derived PCs can be further specified to CD274+ capillary and DLK1+ arteriolar PCs with a proinflammatory and contractile phenotype, respectively. SMC maturation was induced using a MEK inhibitor. Establishing the vasculogenic lineage tree, along with identification of stage- and lineage-specific markers, provides a platform for interrogating the molecular mechanisms that regulate vasculogenic cell specification and diversification and manufacturing well-defined mural cell populations for vascular engineering and cellular therapies from hPSCs.

KEYWORDS:

development; mesenchymoangioblast; pericytes; pluripotent stem cells; smooth muscles

PMID:
28564607
PMCID:
PMC6428685
DOI:
10.1016/j.celrep.2017.05.019
[Indexed for MEDLINE]
Free PMC Article

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