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Specification of functional neurons and glia from human pluripotent stem cells

机译:人多能干细胞功能神经元和胶质细胞的规格

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Human pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold great promise in regenerative medicine as they are an important source of functional cells for potential cell replacement. These human PSCs, similar to their counterparts of mouse, have the full potential to give rise to any type of cells in the body. However, for the promise to be fulfilled, it is necessary to convert these PSCs into functional specialized cells. Using the developmental principles of neural lineage specification, human ESCs and iPSCs have been effectively differentiated to regional and functional specific neurons and glia, such as striatal gama-aminobutyric acid ( GABA )-ergic neurons, spinal motor neurons and myelin sheath forming oligodendrocytes. The human PSCs, in general differentiate after the similar developmental program as that of the mouse: they use the same set of cell signaling to tune the cell fate and they share a conserved transcriptional program that directs the cell fate transition. However, the human PSCs, unlike their counterparts of mouse, tend to respond divergently to the same set of extracellular signals at certain stages of differentiation, which will be a critical consideration to translate the animal model based studies to clinical application.
机译:人类多能干细胞(PSC),如胚胎干细胞(ESC)和诱导性多能干细胞(iPSC)在再生医学中具有广阔的前景,因为它们是功能性细胞替代潜在细胞的重要来源。这些人类PSC与小鼠类似,具有产生体内任何类型细胞的全部潜力。但是,为了兑现承诺,有必要将这些PSC转换为功能专门的单元。使用神经谱系规范的发展原理,人类胚胎干细胞和iPSCs已有效地区分到区域和功能特定的神经元和神经胶质细胞,例如纹状体gama-氨基丁酸(GABA)-能动神经元,脊髓运动神经元和髓鞘形成少突胶质细胞。通常,人类PSC在与小鼠相似的发育程序后得以区分:它们使用同一组细胞信号转导来调节细胞命运,并且它们共享指导细胞命运过渡的保守转录程序。然而,与小鼠的对应物不同,人类PSC在分化的某些阶段倾向于对同一组细胞外信号产生不同的反应,这将是将基于动物模型的研究转化为临床应用的关键考虑因素。

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