Pericytes (PCs) are a type of perivascular cells that surround endothelial cells of small blood vessels. In the brain, PCs show heterogeneity depending on their position within the vasculature. As a result, PC interactions with surrounding endothelial cells, astrocytes, and neuron cells play a key role in a wide array of neurovascular functions such as regulating blood–brain barrier (BBB) permeability, cerebral blood flow, and helping to facilitate the clearance of toxic cellular molecules. Therefore, a reliable method of engineering brain-specific PCs from human induced pluripotent stem cells (hiPSCs) is critical in neurodegenerative disease modeling. This review summarizes brain-specific PC differentiation of hiPSCs through mesoderm and neural crest induction. Key signaling pathways (platelet-derived growth factor-B [PDGF-B], transforming growth factor [TGF]-β, and Notch signaling) regulating PC function, PC interactions with adjacent cells, and PC differentiation from hiPSCs are also discussed. Specifically, PDGF-BB-platelet-derived growth factor receptor β signaling promotes PC cell survival, TGF-β signal transduction facilitates PC attachment to endothelial cells, and Notch signaling is critical in vascular development and arterial-venous specification. Furthermore, current challenges facing the use of hiPSC-derived PCs are discussed, and their ongoing uses in neurodegenerative disease modeling are identified. Further investigations into PCs and surrounding cell interactions are needed to characterize the roles of brain PCs in various neurodegenerative disorders.

中文翻译：

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从人类多能干细胞中工程化脑特异性周细胞。


周细胞（PC）是一种围绕小血管内皮细胞的血管周围细胞。在大脑中，PC 表现出异质性，具体取决于它们在脉管系统中的位置。因此，PC 与周围内皮细胞、星形胶质细胞和神经元细胞的相互作用在多种神经血管功能中发挥着关键作用，例如调节血脑屏障 (BBB) 通透性、脑血流量，并有助于促进有毒的细胞分子。因此，从人类诱导多能干细胞 (hiPSC) 中工程化脑特异性 PC 的可靠方法对于神经退行性疾病建模至关重要。本综述总结了 hiPSC 通过中胚层和神经嵴诱导进行的脑特异性 PC 分化。还讨论了调节 PC 功能、PC 与邻近细胞的相互作用以及 PC 从 hiPSC 分化的关键信号传导途径（血小板衍生生长因子-B [PDGF-B]、转化生长因子 [TGF]-β 和 Notch 信号传导）。具体来说，PDGF-BB-血小板衍生的生长因子受体β信号传导促进PC细胞存活，TGF-β信号转导促进PC附着于内皮细胞，而Notch信号传导在血管发育和动静脉规范中至关重要。此外，还讨论了当前使用 hiPSC 衍生 PC 面临的挑战，并确定了它们在神经退行性疾病模型中的持续应用。需要进一步研究 PC 和周围细胞的相互作用，以表征大脑 PC 在各种神经退行性疾病中的作用。