Extensive transcriptional and chromatin changes underlie astrocyte maturation in vivo and in culture

Michael Lattke, Robert Goldstone, James K. Ellis, Stefan Boeing, Jerónimo Jurado-Arjona, Nicolás Marichal, James I. MacRae, Benedikt Berninger and Francois Guillemot ()
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Michael Lattke: The Francis Crick Institute
Robert Goldstone: The Francis Crick Institute
James K. Ellis: The Francis Crick Institute
Stefan Boeing: The Francis Crick Institute
Jerónimo Jurado-Arjona: King’s College London
Nicolás Marichal: King’s College London
James I. MacRae: The Francis Crick Institute
Benedikt Berninger: King’s College London
Francois Guillemot: The Francis Crick Institute

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract Astrocytes have essential functions in brain homeostasis that are established late in differentiation, but the mechanisms underlying the functional maturation of astrocytes are not well understood. Here we identify extensive transcriptional changes that occur during murine astrocyte maturation in vivo that are accompanied by chromatin remodelling at enhancer elements. Investigating astrocyte maturation in a cell culture model revealed that in vitro-differentiated astrocytes lack expression of many mature astrocyte-specific genes, including genes for the transcription factors Rorb, Dbx2, Lhx2 and Fezf2. Forced expression of these factors in vitro induces distinct sets of mature astrocyte-specific transcripts. Culturing astrocytes in a three-dimensional matrix containing FGF2 induces expression of Rorb, Dbx2 and Lhx2 and improves astrocyte maturity based on transcriptional and chromatin profiles. Therefore, extrinsic signals orchestrate the expression of multiple intrinsic regulators, which in turn induce in a modular manner the transcriptional and chromatin changes underlying astrocyte maturation.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24624-5

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DOI: 10.1038/s41467-021-24624-5

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