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Ohlig, S. ; Clavreul, S. ; Thorwirth, M. ; Simon-Ebert, T. ; Bocchi, R. ; Ulbricht, S. ; Kannayian, N.* ; Rossner, M.J.* ; Sirko, S. ; Smialowski, P. ; Fischer-Sternjak, J. ; Götz, M.

Molecular diversity of diencephalic astrocytes reveals adult astrogenesis regulated by Smad4.

EMBO J.:e107532 (2021)

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Astrocytes regulate brain-wide functions and also show region-specific differences, but little is known about how general and region-specific functions are aligned at the single-cell level. To explore this, we isolated adult mouse diencephalic astrocytes by ACSA-2-mediated magnetic-activated cell sorting (MACS). Single-cell RNA-seq revealed 7 gene expression clusters of astrocytes, with 4 forming a supercluster. Within the supercluster, cells differed by gene expression related to ion homeostasis or metabolism, with the former sharing gene expression with other regions and the latter being restricted to specific regions. All clusters showed expression of proliferation-related genes, and proliferation of diencephalic astrocytes was confirmed by immunostaining. Clonal analysis demonstrated low level of astrogenesis in the adult diencephalon, but not in cerebral cortex grey matter. This led to the identification of Smad4 as a key regulator of diencephalic astrocyte in vivo proliferation and in vitro neurosphere formation. Thus, astrocytes show diverse gene expression states related to distinct functions with some subsets being more widespread while others are more regionally restricted. However, all share low-level proliferation revealing the novel concept of adult astrogenesis in the diencephalon.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Astrocytes ; Cerebral Cortex ; De Novo Astrocyte Generation ; Proliferation ; Smad4; Neural Stem-cells; In-vivo; Gene-expression; Transcription Factors; Ependymal Cells; Messenger-rna; Mlc1 Protein; Radial Glia; Neurogenesis; Progenitor

ISSN (print) / ISBN 0261-4189

e-ISSN 1460-2075

Journal EMBO Journal, The

Quellenangaben Article Number: e107532

Publisher Wiley

Publishing Place Heidelberg, Germany

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Stem Cell Research (ISF)