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Bai, X.* ; Zhao, N.* ; Koupourtidou, C. ; Fang, L.P.* ; Schwarz, V. ; Caudal, L.C.* ; Zhao, R.* ; Hirrlinger, J.* ; Walz, W.* ; Bian, S.* ; Huang, W.* ; Ninkovic, J. ; Kirchhoff, F.* ; Scheller, A.*

In the mouse cortex, oligodendrocytes regain a plastic capacity, transforming into astrocytes after acute injury.

Dev. Cell 58, 1153-1169.e5 (2023)
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Acute brain injuries evoke various response cascades directing the formation of the glial scar. Here, we report that acute lesions associated with hemorrhagic injuries trigger a re-programming of oligodendrocytes. Single-cell RNA sequencing highlighted a subpopulation of oligodendrocytes activating astroglial genes after acute brain injuries. By using PLP-DsRed1/GFAP-EGFP and PLP-EGFPmem/GFAP-mRFP1 transgenic mice, we visualized this population of oligodendrocytes that we termed AO cells based on their concomitant activity of astro- and oligodendroglial genes. By fate mapping using PLP- and GFAP-split Cre complementation and repeated chronic in vivo imaging with two-photon laser-scanning microscopy, we observed the conversion of oligodendrocytes into astrocytes via the AO cell stage. Such conversion was promoted by local injection of IL-6 and was diminished by IL-6 receptor-neutralizing antibody as well as by inhibiting microglial activation with minocycline. In summary, our findings highlight the plastic potential of oligodendrocytes in acute brain trauma due to microglia-derived IL-6.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Il-6 ; Acute Brain Injury ; Astrocyte ; Differentiation ; Fate Switch ; Oligodendrocyte; Fibrillary Acidic Protein; Cell Fate Determination; Central-nervous-system; Ng2 Glia; Progenitor Cells; Nmda Receptors; White-matter; Stem-cells; Differentiation; Lineage
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Journal Developmental Cell
Quellenangaben Volume: 58, Issue: 13, Pages: 1153-1169.e5 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
POF-Topic(s) 30204 - Cell Programming and Repair
Research field(s) Stem Cell and Neuroscience
PSP Element(s) G-500800-001
Grants
University of Saarland
European Commission
BMBF (EraNet-Neuron BrIE)
Deutsche Forschungsgemeinschaft
DOI 10.1016/j.devcel.2023.04.016
WOS ID 001040482400001
Scopus ID 85163157779
PubMed ID 37220747
Erfassungsdatum 2023-10-06
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