Generation of Embryonic Origin-Specific Vascular Smooth Muscle Cells from Human Induced Pluripotent Stem Cells.

Generation of Embryonic Origin-Specific Vascular Smooth Muscle Cells from Human Induced Pluripotent Stem Cells.

Vascular smooth muscle cells (VSMCs), a highly mosaic tissue, arise from multiple distinct embryonic origins and populate different regions of our vascular network with defined boundaries. Accumulating evidence has revealed that the heterogeneity of VSMC origins contributes to region-specific vascular diseases such as atherosclerosis and aortic aneurysm. These findings highlight the necessity of taking into account lineage-dependent responses of VSMCs to common vascular risk factors when studying vascular diseases. This chapter describes a reproducible, stepwise protocol for the generation of isogenic VSMC subtypes originated from proepicardium, second heart field, cardiac neural crest, and ventral somite using human induced pluripotent stem cells. By leveraging this robust induction protocol, patient-derived VSMC subtypes of desired embryonic origins can be generated for disease modeling as well as drug screening and development for vasculopathies with regional susceptibility.

血管平滑肌细胞（VSMCs）是一种高度嵌合的组织，来源于多种不同的胚胎起源，并分布在我们血管网络的不同区域，且边界明确。越来越多的证据表明，VSMC起源的异质性导致了特定区域的血管疾病，如动脉粥样硬化和主动脉瘤。这些发现凸显了在研究血管疾病时考虑VSMCs对常见血管危险因素的谱系依赖性反应的必要性。本章描述了一种可重复的、逐步的方案，用于利用人类诱导多能干细胞生成源自心外膜原基、第二心区、心脏神经嵴和腹侧体节的同基因VSMC亚型。通过利用这种可靠的诱导方案，可以生成具有所需胚胎起源的患者来源的VSMC亚型，用于疾病建模以及针对具有区域易感性的血管病变进行药物筛选和开发。