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Molecular diversity of diencephalic astrocytes reveals adult astrogenesis regulated by Smad4.
EMBO J.:e107532 (2021)
Verlagsversion
DOI
PMC
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
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
Zeitschrift
EMBO Journal, The
Quellenangaben
Artikelnummer: e107532
Verlag
Wiley
Verlagsort
Heidelberg, Germany
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Stem Cell Research (ISF)
Förderungen
Deutsche Forschungsgemeinschaft (DFG)
EC | H2020 | H2020 Priority Excellent Science | H2020 Future and Emerging Technologies (FET)
EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)
EC | H2020 | H2020 Priority Excellent Science | H2020 Future and Emerging Technologies (FET)
EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)