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


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 PDGFR?+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.

SUBMITTER: Kumar A 

PROVIDER: S-EPMC6428685 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Kumar Akhilesh A   D'Souza Saritha Sandra SS   Moskvin Oleg V OV   Toh Huishi H   Wang Bowen B   Zhang Jue J   Swanson Scott S   Guo Lian-Wang LW   Thomson James A JA   Slukvin Igor I II  

Cell reports 20170501 9


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<sup>+</  ...[more]

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