Functionally distinct subgroups of oligodendrocyte precursor cells integrate neural activity and execute myelin formation

Nat Neurosci. 2020 Mar;23(3):363-374. doi: 10.1038/s41593-019-0581-2. Epub 2020 Feb 17.


Recent reports have revealed that oligodendrocyte precursor cells (OPCs) are heterogeneous. It remains unclear whether such heterogeneity reflects different subtypes of cells with distinct functions or instead reflects transiently acquired states of cells with the same function. By integrating lineage formation of individual OPC clones, single-cell transcriptomics, calcium imaging and neural activity manipulation, we show that OPCs in the zebrafish spinal cord can be divided into two functionally distinct groups. One subgroup forms elaborate networks of processes and exhibits a high degree of calcium signaling, but infrequently differentiates despite contact with permissive axons. Instead, these OPCs divide in an activity- and calcium-dependent manner to produce another subgroup, with higher process motility and less calcium signaling and that readily differentiates. Our data show that OPC subgroups are functionally diverse in their response to neurons and that activity regulates the proliferation of a subset of OPCs that is distinct from the cells that generate differentiated oligodendrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Calcium Signaling / physiology
  • Cell Differentiation
  • Cell Division
  • Cell Lineage
  • Cell Proliferation
  • Embryo, Nonmammalian / physiology
  • Myelin Sheath / physiology*
  • Nerve Net / cytology
  • Nerve Net / physiology
  • Oligodendrocyte Precursor Cells / physiology*
  • Spinal Cord / cytology
  • Spinal Cord / physiology
  • Swimming / physiology
  • Zebrafish