Derivation of telencephalic oligodendrocyte progenitors from human pluripotent stem cells.
Derivation of telencephalic oligodendrocyte progenitors from human pluripotent stem cells.
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DOI：
10.1002/cpsc.17
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发表时间：
2017-11-08
影响因子：
--
通讯作者：
Tabar, Viviane
中科院分区：
文献类型：
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作者：
Major, Tamara;Powers, Ann;Tabar, Viviane
少突胶质细胞是成人中枢神经系统的主要髓鞘细胞，在脊髓损伤、中风、创伤、药物和辐射毒性以及神经炎症等多种疾病中易受损伤。人多能干细胞是诱人的少突胶质细胞系细胞来源，为通过移植修复外源性髓鞘提供了一种有前景的治疗策略。本单位描述了一种在特定的化学体外培养条件下，从人类多能干细胞中逐步分化出前脑晚期少突胶质前体细胞(OPC)的方案。它涉及少突胶质前体细胞在其已知发育阶段的逐步发展，从适当的转录因子(Opol2，Nkx2.2)的表达开始，PDGFRA上调，随后出现表达O4的细胞，然后表达O1，最后表达成熟的髓鞘结合蛋白(MBP)的细胞。细胞命运的验证是通过广泛的转录图谱以及hESCs来源的神经元细胞的体外髓鞘形成试验来进行的。概括前脑少突胶质细胞的发育可能会产生更适合移植策略的细胞，主要涉及端脑。
Oligodendrocytes are the main myelinating cell of the adult CNS and are vulnerable to injury in diverse disorders such as spinal cord injury, stroke, trauma, pharmacological and radiation toxicity, as well as neuroinflammation. Human pluripotent stem cells are attractive sources of oligodendrocyte lineage cells and provide a promising treatment strategy for exogenous myelin repair through transplantation. This unit describes a protocol for the step-wise differentiation of forebrain late oligodendrocyte progenitor cells (OPCs) from human pluripotent stem cells in defined chemical in vitro culture conditions. It involves a stepwise progression of oligodendrocyte progenitors through their known developmental phases, starting with the expression of appropriate transcription factors (Olig2, Nkx2.2), the upregulation of PDGFRA, followed by the appearance of O4-expressing cells, then O1 expression and finally mature myelin-binding protein (MBP) expressing cells. Validation of cell fate is performed by extensive transcriptomal profiling, as well in vitro myelination essays with hESCs derived neuronal cells. Recapitulating forebrain oligodendrocyte development may generate cells more suitable for transplantation strategies for disorders primarily involving the telencephalon.