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

Xianshu Bai; Na Zhao; Christina Koupourtidou; Li-Pao Fang; Veronika Schwarz; Laura C Caudal; Renping Zhao; Johannes Hirrlinger; Wolfgang Walz; Shan Bian; Wenhui Huang; Jovica Ninkovic; Frank Kirchhoff; Anja Scheller

doi:10.1016/j.devcel.2023.04.016

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

Dev Cell. 2023 Jul 10;58(13):1153-1169.e5. doi: 10.1016/j.devcel.2023.04.016. Epub 2023 May 22.

Authors

Affiliations

¹ Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, 66421 Homburg, Germany. Electronic address: xianshu.bai@uks.eu.
² Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, 66421 Homburg, Germany.
³ Department of Cell Biology and Anatomy, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany; Institute of Stem Cell Research, Helmholtz Zentrum Munich, 85764 Neuherberg-Munich, Germany.
⁴ Carl-Ludwig-Institute for Physiology, Leipzig University, 04103 Leipzig, Germany; Department of Neurogenetics, Max-Planck-Institute for Multidisciplinary Sciences, 37075 Göttingen, Germany.
⁵ Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, 66421 Homburg, Germany; Department of Psychiatry, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
⁶ Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, 200092 Shanghai, China; Frontier Science Center for Stem Cell Research, Tongji University, 200092 Shanghai, China.
⁷ Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, 66421 Homburg, Germany; Experimental Research Center for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
⁸ Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, 66421 Homburg, Germany. Electronic address: anja.scheller@uks.eu.

PMID: 37220747
DOI: 10.1016/j.devcel.2023.04.016

Abstract

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-EGFP_mem/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.

Keywords: IL-6; acute brain injury; astrocyte; differentiation; fate switch; oligodendrocyte.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes*
Brain Injuries*
Glial Fibrillary Acidic Protein / genetics
Interleukin-6
Mice
Mice, Transgenic
Oligodendroglia

Substances

Interleukin-6
Glial Fibrillary Acidic Protein