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

• Published in: Nature neuroscience Vol. 23; no. 3; pp. 363 - 374
• Main Authors: Marisca, Roberta, Hoche, Tobias, Agirre, Eneritz, Hoodless, Laura Jane, Barkey, Wenke, Auer, Franziska, Castelo-Branco, Gonçalo, Czopka, Tim
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2020; Nature Publishing Group
• Subjects: 631/378/2571; 631/378/2596; 631/378/2606; Animal Genetics and Genomics; Animals; Animals, Genetically Modified; Axons; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Calcium; Calcium imaging; Calcium Signaling - physiology; Calcium signalling; Cell Differentiation; Cell Division; Cell Lineage; Cell Proliferation; Danio rerio; Embryo, Nonmammalian - physiology; External stimuli; Gene expression; Glial stem cells; Heterogeneity; Medicin och hälsovetenskap; Multiple sclerosis; Myelin; Myelin proteins; Myelin Sheath - physiology; Nerve Net - cytology; Nerve Net - physiology; Neural circuitry; Neurobiology; Neuroglia; Neurosciences; Observations; Oligodendrocyte Precursor Cells - physiology; Oligodendrocytes; Physiological aspects; Physiology; Precursors; Properties; Signaling; Spinal cord; Spinal Cord - cytology; Spinal Cord - physiology; Subgroups; Swimming - physiology; Zebrafish; Germany
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-019-0581-2

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. Oligodendrocyte precursor cells divide or differentiate in response to external stimuli to control their numbers and to form new myelin. Using zebrafish, we show that these two functions are accomplished by distinct subgroups of cells.