A molecularly defined subpopulation of oligodendrocyte precursor cells controls the generation of myelinating oligodendrocytes during postnatal development

PLoS Biol. 2024 Jul 10;22(7):e3002655. doi: 10.1371/journal.pbio.3002655. eCollection 2024 Jul.

Abstract

Oligodendrocyte precursor cells (OPCs) are a class of glial cells that uniformly tiles the entire central nervous system (CNS). They play several key functions across the brain including the generation of oligodendrocytes and the control of myelination. Whether the functional diversity of OPCs is the result of genetically defined subpopulations or of their regulation by external factors has not been definitely established. We discovered that a subpopulation of OPCs found across the brain is defined by the expression of C1ql1, a gene previously described for its synaptic function in neurons. This subpopulation starts to appear during the first postnatal week in the mouse cortex. Ablation of C1ql1-expressing OPCs in the mouse leads to a massive lack of oligodendrocytes and myelination in many brain regions. This deficit cannot be rescued, even though some OPCs escape Sox10-driven ablation and end up partially compensating the OPC loss in the adult. Therefore, C1ql1 is a molecular marker of a functionally non-redundant subpopulation of OPCs, which controls the generation of myelinating oligodendrocytes.

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / growth & development
  • Brain / metabolism
  • Cell Differentiation / genetics
  • Gene Expression Regulation, Developmental
  • Mice
  • Myelin Sheath* / metabolism
  • Oligodendrocyte Precursor Cells* / cytology
  • Oligodendrocyte Precursor Cells* / metabolism
  • Oligodendroglia* / cytology
  • Oligodendroglia* / metabolism

Grants and funding

This work was supported by funding from: European Research Council ERC consolidator grant SynID 724601 (to FS; https://erc.europa.eu/homepage), Agence Nationale de la Recherche (ANR) MEMO LIFE grant ANR-10-LABX-54 (to FS; https://www.memolife.bio.ens.psl.eu/), Institut National du Cancer (INCA) grant PEDIAHR21-014 (to FS; https://en.e-cancer.fr/). SM received a PhD thesis funding from la Ligue Nationale Contre le Cancer (https://www.ligue-cancer.net/) and Ecole des neurosciences de Paris Ile-de-France (ENP). Since 2019, ENP has changed to la Fondation des Neurosciences Paris (FNP, https://www.sorbonne-universite.fr/universite/fondation-sorbonne-universite/fondation-abritee-fondation-des-neurosciences-de-paris). The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.