Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system

TLDR

Oligodendrocytes were previously regarded as a functionally homogeneous population in the central nervous system. Single‑cell RNA sequencing of 5,072 oligodendrocyte‑lineage cells from ten regions of juvenile and adult mouse CNS was performed. The analysis uncovered 13 distinct oligodendrocyte populations, revealing a continuum from OPCs to mature cells, region‑specific mature subsets in adults, newly formed cells responsive to motor learning, a vessel‑associated Pdgfra⁺ population, and transcriptionally uncoupled differentiation and maturation that highlight CNS oligodendrocyte heterogeneity.

Abstract

Oligodendrocytes have been considered as a functionally homogeneous population in the central nervous system (CNS). We performed single-cell RNA sequencing on 5072 cells of the oligodendrocyte lineage from 10 regions of the mouse juvenile and adult CNS. Thirteen distinct populations were identified, 12 of which represent a continuum from Pdgfra(+) oligodendrocyte precursor cells (OPCs) to distinct mature oligodendrocytes. Initial stages of differentiation were similar across the juvenile CNS, whereas subsets of mature oligodendrocytes were enriched in specific regions in the adult brain. Newly formed oligodendrocytes were detected in the adult CNS and were responsive to complex motor learning. A second Pdgfra(+) population, distinct from OPCs, was found along vessels. Our study reveals the dynamics of oligodendrocyte differentiation and maturation, uncoupling them at a transcriptional level and highlighting oligodendrocyte heterogeneity in the CNS.