Fast Generation of Functional Subtype Astrocytes from Human Pluripotent Stem Cells
| Autor: | Xiang Li, Zhongwei Du, Yuanwei Yan, Su-Chun Zhang, Yunlong Tao, Linghai Kong, Lindsay Morgan Friedman, Magd Bilal, Brianna Hoffmann, Cole R. K. Harder, Yi Dong, Jeffrey P. Jones, Yezheng Tao, Robert A. Bradley |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pluripotent Stem Cells Transgene Neuronal Outgrowth fast astrocyte differentiation SOX9 transplantable astrocytes Biology Biochemistry Article subtype astrocytes fast differentiation from hPSCs 03 medical and health sciences CRISPR/Cas9 induced differentiation Genetics medicine CRISPR Humans Progenitor cell Induced pluripotent stem cell lcsh:QH301-705.5 lcsh:R5-920 engineering hPSCs Cell Differentiation SOX9 Transcription Factor Cell Biology functional astrocytes Cell biology NFIA Transplantation NFI Transcription Factors 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Astrocytes lcsh:Medicine (General) human astrocytes Developmental Biology Astrocyte |
| Zdroj: | Stem Cell Reports Stem Cell Reports, Vol 11, Iss 4, Pp 998-1008 (2018) |
| ISSN: | 2213-6711 |
| Popis: | 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. Graphical Abstract Highlights • Fast differentiation of astrocytes from human pluripotent stem cells (hPSCs) • NFIA or NFIA plus SOX9 overexpression facilitates astrocyte generation • Fast generation of subtype-specific astrocytes from hPSCs • CRISPR/Cas9-engineered hPSCs for fast generation of astrocytes In this article, Zhang and colleagues show that functional and subtype-specific astrocytes can be fast generated from hPSCs by using CRISPR/Cas9-mediated inducible expression of NFIA or NFIA plus SOX9 in hPSCs. This simple and efficient method offers the opportunity to study the fundamental biology of human astrocytes and their roles in disease processes. |
| Databáze: | OpenAIRE |
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