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Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts
Author(s) -
Akhilesh Kumar,
Saritha S. D’Souza,
Oleg V. Moskvin,
Huishi Toh,
Bowen Wang,
Jue Zhang,
Scott Swanson,
Lian-Wang Guo,
James A. Thomson,
Igor I. Slukvin
Publication year - 2017
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2017.05.019
Subject(s) - mesenchymal stem cell , biology , microbiology and biotechnology , progenitor cell , mural cell , pericyte , induced pluripotent stem cell , stem cell , mesoderm , stromal cell , vascular smooth muscle , endothelial stem cell , immunology , cancer research , embryonic stem cell , genetics , smooth muscle , endocrinology , in vitro , gene
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.

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