Heterogeneity in oligodendrocyte precursor cell proliferation is dynamic and driven by passive bioelectrical properties
Helena Pivoňková,
Sergey Sitnikov,
Yasmine Kamen,
An Vanhaesebrouck,
Moritz Matthey,
Sonia Olivia Spitzer,
Yan Ting Ng,
Chenyue Tao,
Omar de Faria, Jr.,
Balazs Viktor Varga,
Ragnhildur Thóra Káradóttir
Affiliations
Helena Pivoňková
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK
Sergey Sitnikov
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK
Yasmine Kamen
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK
An Vanhaesebrouck
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK
Moritz Matthey
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK
Sonia Olivia Spitzer
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK
Yan Ting Ng
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK
Chenyue Tao
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK
Omar de Faria, Jr.
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK
Balazs Viktor Varga
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK
Ragnhildur Thóra Káradóttir
Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge CB2 0AW, UK; Department of Physiology, BioMedical Center, Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland; Corresponding author
Summary: Oligodendrocyte precursor cells (OPCs) generate myelinating oligodendrocytes and are the main proliferative cells in the adult central nervous system. OPCs are a heterogeneous population, with proliferation and differentiation capacity varying with brain region and age. We demonstrate that during early postnatal maturation, cortical, but not callosal, OPCs begin to show altered passive bioelectrical properties, particularly increased inward potassium (K+) conductance, which correlates with G1 cell cycle stage and affects their proliferation potential. Neuronal activity-evoked transient K+ currents in OPCs with high inward K+ conductance potentially release OPCs from cell cycle arrest. Eventually, OPCs in all regions acquire high inward K+ conductance, the magnitude of which may underlie differences in OPC proliferation between regions, with cells being pushed into a dormant state as they acquire high inward K+ conductance and released from dormancy by synchronous neuronal activity. Age-related accumulation of OPCs with high inward K+ conductance might contribute to differentiation failure.
