Department of Biotechnology, Korea University, Seoul, Korea.
Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Korea.
J Cell Physiol. 2021 Nov;236(11):7625-7641. doi: 10.1002/jcp.30405. Epub 2021 May 5.
The ability to generate astrocytes from human pluripotent stem cells (hPSCs) offers a promising cellular model to study the development and physiology of human astrocytes. The extant methods for generating functional astrocytes required long culture periods and there remained much ambiguity on whether such paradigms follow the innate developmental program. In this report, we provided an efficient and rapid method for generating physiologically functional astrocytes from hPSCs. Overexpressing the nuclear factor IB in hPSC-derived neural precursor cells induced a highly enriched astrocyte population in 2 weeks. RNA sequencing and functional analyses demonstrated progressive transcriptomic and physiological changes in the cells, resembling in vivo astrocyte development. Further analyses substantiated previous results and established the MAPK pathway necessary for astrocyte differentiation. Hence, this differentiation paradigm provides a prospective in vitro model for human astrogliogenesis studies and the pathophysiology of neurological diseases concerning astrocytes.
从人类多能干细胞（hPSCs）中产生星形胶质细胞的能力为研究人类星形胶质细胞的发育和生理学提供了一个很有前途的细胞模型。现有的产生功能性星形胶质细胞的方法需要很长的培养时间，而且对于这些模型是否遵循内在的发育程序仍然存在很大的不确定性。在本报告中，我们提供了一种从 hPSCs 中高效快速产生生理功能星形胶质细胞的方法。在 hPSC 衍生的神经前体细胞中过表达核因子 IB 可在 2 周内诱导出高度富集的星形胶质细胞群体。RNA 测序和功能分析表明，细胞中的转录组和生理变化呈渐进式，类似于体内星形胶质细胞的发育。进一步的分析证实了先前的结果，并确定了 MAPK 通路对于星形胶质细胞分化是必需的。因此，这种分化模型为人类星形胶质细胞发生的研究和涉及星形胶质细胞的神经疾病的病理生理学提供了一个有前景的体外模型。
