[PDF][PDF] Specification and diversification of pericytes and smooth muscle cells from mesenchymoangioblasts

A Kumar, SS D'Souza, OV Moskvin, H Toh, B Wang… - Cell reports, 2017 - cell.com
A Kumar, SS D'Souza, OV Moskvin, H Toh, B Wang, J Zhang, S Swanson, LW Guo
Cell reports, 2017cell.com
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 …
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.
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