Single-cell approaches define two groups of mammalian oligodendrocyte precursor cells and their evolution over developmental time

Daniel J Dennis; Beatrix S Wang; Konstantina Karamboulas; David R Kaplan; Freda D Miller

doi:10.1016/j.stemcr.2024.03.002

Single-cell approaches define two groups of mammalian oligodendrocyte precursor cells and their evolution over developmental time

Stem Cell Reports. 2024 Mar 22:S2213-6711(24)00077-8. doi: 10.1016/j.stemcr.2024.03.002. Online ahead of print.

Authors

Daniel J Dennis¹, Beatrix S Wang², Konstantina Karamboulas¹, David R Kaplan³, Freda D Miller⁴

Affiliations

¹ Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
² Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
³ Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
⁴ Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Electronic address: freda.miller@msl.ubc.ca.

PMID: 38579710
DOI: 10.1016/j.stemcr.2024.03.002

Abstract

Here, we used single-cell RNA sequencing (scRNA-seq), single-cell ATAC sequencing (scATAC-seq), and single-cell spatial transcriptomics to characterize murine cortical OPCs throughout postnatal life. During development, we identified two groups of differentially localized PDGFRα⁺ OPCs that are transcriptionally and epigenetically distinct. One group (active, or actOPCs) is metabolically active and enriched in white matter. The second (homeostatic, or hOPCs) is less active, enriched in gray matter, and predicted to derive from actOPCs. In adulthood, these two groups are transcriptionally but not epigenetically distinct, and relative to developing OPCs are less active metabolically and have less open chromatin. When adult oligodendrogenesis is enhanced during experimentally induced remyelination, adult OPCs do not reacquire a developmental open chromatin state, and the oligodendrogenesis trajectory is distinct from that seen neonatally. These data suggest that there are two OPC groups subserving distinct postnatal functions and that neonatal and adult OPC-mediated oligodendrogenesis are fundamentally different.

Keywords: brain development; corpus callosum; cortex; myelin; oligodendrocyte; oligodendrocyte precursor cell; remyelination; scATAC-seq; scRNA-seq; single cell spatial transcriptomics; white matter injury.