Kumar Akhilesh, D'Souza Saritha Sandra, Moskvin Oleg V, Toh Huishi, Wang Bowen, Zhang Jue, Swanson Scott, Guo Lian-Wang, Thomson James A, Slukvin Igor I
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA.
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53703, USA.
Cell Rep. 2017 May 30;19(9):1902-1916. doi: 10.1016/j.celrep.2017.05.019.
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 PDGFRβCD271CD73 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.
阐明导致血管生成细胞的途径，并能够识别它们的祖细胞和谱系受限细胞，对于建立用于血管疾病的人类多能干细胞（hPSC）模型以及开发血管治疗方法至关重要。在这里，我们发现中胚层来源的周细胞（PCs）和平滑肌细胞（SMCs）起源于克隆性间充质祖细胞间充质血管母细胞（MB）。在克隆形成培养中，MB分化为原始的PDGFRβCD271CD73间充质祖细胞，后者产生增殖性PCs、SMCs和间充质干/基质细胞。MB来源的PCs可以进一步分别分化为具有促炎和收缩表型的CD274毛细血管PCs和DLK1小动脉PCs。使用MEK抑制剂诱导SMC成熟。建立血管生成谱系树，以及识别阶段和谱系特异性标志物，为探究调节血管生成细胞特化和多样化的分子机制以及从hPSC制造用于血管工程和细胞治疗的明确壁细胞群体提供了一个平台。
