Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system.
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.
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Sueli
S
Marques
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Amit
A
Zeisel
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.|Department of Physiology and Pharmacology, Karolinska Institutet SE-17177 Stockholm, Sweden.
Simone
S
Codeluppi
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
David
D
van Bruggen
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Ana
A
Mendanha Falcão
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom.|Institute of Neuroscience, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Lin
L
Xiao
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Huiliang
H
Li
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Martin
M
Häring
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Hannah
H
Hochgerner
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.|Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Austria.
Roman A
RA
Romanov
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Daniel
D
Gyllborg
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Ana
A
Muñoz Manchado
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Gioele
G
La Manno
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Peter
P
Lönnerberg
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Elisa M
EM
Floriddia
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Fatemah
F
Rezayee
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Patrik
P
Ernfors
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Ernest
E
Arenas
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Jens
J
Hjerling-Leffler
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.|Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Austria.
Tibor
T
Harkany
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom.
William D
WD
Richardson
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Sten
S
Linnarsson
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Gonçalo
G
Castelo-Branco
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000254:growth & development*; D019070:Cell Lineage; D002478:Cells, Cultured; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D007858:Learning / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D015415:Biomarkers; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011509:Proteoglycans; D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000099216:Chondroitin Sulfate Proteoglycan 4