近轴中胚层
中胚层
神经外胚层
生物
诱导多能干细胞
侧板中胚层
细胞生物学
血管平滑肌
节的
细胞外基质
解剖
胚胎干细胞
遗传学
平滑肌
内分泌学
基因
作者
Christine Cheung,Andreia S. Bernardo,Matthew Trotter,Roger A. Pedersen,Sanjay Sinha
摘要
Vascular smooth muscle cells have multiple embryological origins. Cheung et al. present a chemically defined protocol for differentiating human pluripotent stem cells into vascular smooth muscle subtypes arising from neuroectoderm, lateral plate mesoderm and paraxial mesoderm. Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs) and may influence the development of vascular disease. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin–specific SMC subtypes remains elusive. Here we describe a chemically defined protocol in which hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated toward SMCs (>80% MYH11+ and ACTA2+), which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Notably, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. This differentiation approach will have broad applications in modeling origin-dependent disease susceptibility and in developing bioengineered vascular grafts for regenerative medicine.
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