Cell Reports
Volume 19, Issue 9, 30 May 2017, Pages 1902-1916
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Article
Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts

https://doi.org/10.1016/j.celrep.2017.05.019Get rights and content
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Highlights

  • Mesodermal mural cells originate from a clonal precursor mesenchymoangioblast (MB)

  • PDGFRβ+CD271+DLK1+CD73 phenotype identifies intermediate mural cell precursors

  • MB-derived pericytes can be specified to capillary and arteriolar types

  • Lineage tree of vasculogenic progenitors in hPSC cultures is proposed

Summary

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

pericytes
smooth muscles
pluripotent stem cells
mesenchymoangioblast
development

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