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通过诱导 hiPSC 衍生的神经板缘细胞进行早期神经嵴发育的建模。

Modeling Early Neural Crest Development via Induction from hiPSC-Derived Neural Plate Border-like Cells.

机构信息

Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.

出版信息

Methods Mol Biol. 2022;2549:281-298. doi: 10.1007/7651_2021_454.

Abstract

Neural crest cells (NCCs) are a multipotent and transient cell population that gives rise to many important tissues during human embryogenesis. Disturbances that occur during NCCs development may lead to numerous types of diseases and syndromes, which are called neurocristopathies. NCCs in vitro modeling enables the access to cellular, genetic, and biochemical information about the neural crest development and its derivatives. By using cells derived from patients with neurocristopathies it is possible to study the cellular and genetic mechanisms behind each disease in a specific and trustworthy manner, as well as to contribute to the development of prospective treatments. Here, we describe a protocol of 19 days, capable of efficiently generating NCCs from human induced pluripotent stem cells (hiPSCs). This differentiation process recapitulates the intermediate stage of neural plate border-like cells (NBCs), the epithelial to mesenchymal transition (EMT), and enables further generation of NCCs derivatives, such as Schwann cells, smooth muscle cells, melanocytes, peripheral neurons, adipocytes, osteoblasts, and chondrocytes.

摘要

神经嵴细胞(NCCs)是一种多能且短暂的细胞群体,在人类胚胎发生过程中产生许多重要的组织。NCCs 发育过程中发生的干扰可能导致多种疾病和综合征,这些疾病和综合征被称为神经嵴病变。体外 NCCs 建模使我们能够获得有关神经嵴发育及其衍生物的细胞、遗传和生化信息。通过使用源自神经嵴病变患者的细胞,可以以特定且可靠的方式研究每种疾病背后的细胞和遗传机制,并为潜在治疗方法的开发做出贡献。在这里,我们描述了一个为期 19 天的方案,能够从人诱导多能干细胞(hiPSC)中有效地生成 NCCs。这个分化过程重现了神经板边界样细胞(NBCs)的中间阶段、上皮到间充质转化(EMT),并能够进一步生成 NCCs 的衍生物,如施万细胞、平滑肌细胞、黑素细胞、周围神经元、脂肪细胞、成骨细胞和软骨细胞。

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