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

Author

Listed:
  • 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
    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
    King’s College London
    University Medical Center of the Johannes Gutenberg University Mainz
    The Francis Crick Institute)

  • Francois Guillemot

    (The Francis Crick Institute)

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.

Suggested Citation

  • Michael Lattke & Robert Goldstone & James K. Ellis & Stefan Boeing & Jerónimo Jurado-Arjona & Nicolás Marichal & James I. MacRae & Benedikt Berninger & Francois Guillemot, 2021. "Extensive transcriptional and chromatin changes underlie astrocyte maturation in vivo and in culture," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24624-5
    DOI: 10.1038/s41467-021-24624-5
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    References listed on IDEAS

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    2. Woo-Ping Ge & Atsushi Miyawaki & Fred H. Gage & Yuh Nung Jan & Lily Yeh Jan, 2012. "Local generation of glia is a major astrocyte source in postnatal cortex," Nature, Nature, vol. 484(7394), pages 376-380, April.
    3. Gil Ron & Yuval Globerson & Dror Moran & Tommy Kaplan, 2017. "Promoter-enhancer interactions identified from Hi-C data using probabilistic models and hierarchical topological domains," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
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    3. Ruohan Wang & Yumin Zheng & Zijian Zhang & Kailu Song & Erxi Wu & Xiaopeng Zhu & Tao P. Wu & Jun Ding, 2024. "MATES: a deep learning-based model for locus-specific quantification of transposable elements in single cell," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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