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Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts
oleh: Akhilesh Kumar, Saritha Sandra D’Souza, Oleg V. Moskvin, Huishi Toh, Bowen Wang, Jue Zhang, Scott Swanson, Lian-Wang Guo, James A. Thomson, Igor I. Slukvin
Format: | Article |
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Diterbitkan: | Elsevier 2017-05-01 |
Deskripsi
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.