Single cell approaches define two mammalian oligodendrocyte precursor cell populations and their evolution over developmental time [Xenium In Situ Gene Expression]

Here, we have used single-cell RNA sequencing (scRNA-seq), single-cell ATAC sequencing (scATAC-seq) and spatial transcriptomics to characterize murine cortical OPCs throughout postnatal life. During development, we identify two differentially-localized PDGFRα-positive OPC populations that are transcriptionally and epigenetically distinct. One population (active or actOPCs) is metabolically active and is enriched in white matter. The second (homeostatic or hOPCs) is less active, enriched in grey 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 with much less open chromatin. When adult oligodendrogenesis is enhanced following experimental demyelination, adult OPCs do not reacquire a developmental open chromatin state, and the oligodendrogenesis trajectory is distinct from that seen neonatally. These data support a model where two OPC populations subserve distinct postnatal functions, and where neonatal and adult OPC-mediated oligodendrogenesis are fundamentally different. Multiplexed in situ hybridization-based spatial transcriptomics using the Xenium platform was used to analyze coronal P7 forebrain sections containing the V-SVZ, corpus callosum and cortex with a probeset that included marker genes for relevant cell types, including actOPCs and hOPCs. We analyzed a region of interest that included the V-SVZ, the corpus callosum and the cortical grey matter from two different brains (2 sections from one brain, 1 section from the other). Replicates are indicated (biol 1, biol 2, biol 3).