Fast Generation of Functional Subtype Astrocytes from Human Pluripotent Stem Cells

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

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  Fast differentiation of astrocytes from human pluripotent stem cells (hPSCs)

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  NFIA or NFIA plus SOX9 overexpression facilitates astrocyte generation

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  Fast generation of subtype-specific astrocytes from hPSCs

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  CRISPR/Cas9-engineered hPSCs for fast generation of astrocytes

Abstract

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.