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Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system.

Science (New York, N.Y.) 2016
Open on PubMed

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.

8 Figures Extracted
Figure 1
Figure 1 PMC
Single cell RNA-Seq analysis of 5072 cells expressing markers of the oligodendrocyte lineage in ten regions of the mouse CNS.
Figure 1
Figure 1 PMC
(A) Targeted regions. (B) Number of cells analysed for each region. (C) Hierarchical clustering (left), correlation matrix (middle) and subclass abund...
Figure 2
Figure 2 PMC
Oligodendrocyte cell states in the continuous maturation process from precursors to mature cells.
Figure 2
Figure 2 PMC
(A) t-SNE projection showing the trajectory from OPCs to mature oligodendrocytes. (B) Average (±s.e.m.) expression of marker genes for OPCs, COPs and ...
Figure 3
Figure 3 PMC
ITPR2+ oligodendrocytes are present in regions of active differentiation and increase in mice undergoing learning in the complex wheel paradigm.
Figure 3
Figure 3 PMC
(A) Average (±s.e.m.) expression level of Tcf7l2, Itpr2, Tmem2 and Pdgfa along the oligodendrocyte lineage. (B-C) Immunohistochemistry and quantificat...
Figure 4
Figure 4 PMC
Region and age specific distribution of mature oligodendrocytes
Figure 4
Figure 4 PMC
(A) t-SNE projections as in Fig. 2A with colored dots representing cells from each of the ten CNS regions analyzed. (B) Age distribution of OL populat...
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