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

Michael Lattke, Robert Goldstone, James K Ellis, Stefan Boeing, Jeronimo Jurado Arjona, Nicolas Marichal Negrin, James I McRae, Benedikt Berninger, Francois Guillemot

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

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.
Original languageEnglish
Article number4335
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2021

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