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Fast Generation of Functional Subtype Astrocytes from Human Pluripotent Stem Cells

机译:从人类多能干细胞快速生成功能性亚型星形胶质细胞

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Summary Differentiation of astrocytes from human pluripotent stem cells (hPSCs) is a tedious and variable process. This hampers the study of hPSC-generated astrocytes in disease processes and drug development. By using CRISPR/Cas9-mediated inducible expression of NFIA or NFIA plus SOX9 in hPSCs, we developed a method to efficiently generate astrocytes in 4–7?weeks. The astrocytic identity of the induced cells was verified by their characteristic molecular and functional properties as well as after transplantation. Furthermore, we developed a strategy to generate region-specific astrocyte subtypes by combining differentiation of regional progenitors and transgenic induction of astrocytes. This simple and efficient method offers a new opportunity to study the fundamental biology of human astrocytes and their roles in disease processes.
机译:小结星形胶质细胞与人多能干细胞(hPSC)的分化是一个繁琐且可变的过程。这阻碍了hPSC生成的星形胶质细胞在疾病过程和药物开发中的研究。通过在hPSC中使用CRISPR / Cas9介导的NFIA或NFIA加SOX9诱导型表达,我们开发了一种在4-7周内有效生成星形胶质细胞的方法。通过其特征性的分子和功能特性以及移植后,验证了诱导细胞的星形细胞身份。此外,我们制定了一种策略,通过结合区域祖细胞的分化和转基因诱导星形胶质细胞来生成区域特异性星形胶质细胞亚型。这种简单而有效的方法为研究人类星形胶质细胞的基本生物学及其在疾病过程中的作用提供了新的机会。

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