Fractalkine signaling regulates oligodendroglial cell genesis from SVZ precursor cells

• Published in: Stem cell reports Vol. 16; no. 8; pp. 1968 - 1984
• Main Authors: Watson, Adrianne E.S., de Almeida, Monique M.A., Dittmann, Nicole L., Li, Yutong, Torabi, Pouria, Footz, Tim, Vetere, Gisella, Galleguillos, Danny, Sipione, Simonetta, Cardona, Astrid E., Voronova, Anastassia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.08.2021; Elsevier
• Subjects: Animals; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cells, Cultured; chemokine; Chemokine CX3CL1 - metabolism; Chemokine CX3CL1 - pharmacology; Cognitive science; CX3C Chemokine Receptor 1 - genetics; CX3C Chemokine Receptor 1 - metabolism; CX3CR1; fractalkine; Gene Expression - drug effects; Lateral Ventricles - cytology; Lateral Ventricles - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Confocal; myelin; neural stem cell; oligodendrocyte; oligodendrocyte precursor; Oligodendrocyte Precursor Cells - cytology; Oligodendrocyte Precursor Cells - metabolism; Oligodendrocyte Transcription Factor 2 - genetics; Oligodendrocyte Transcription Factor 2 - metabolism; Oligodendroglia - cytology; Oligodendroglia - metabolism; OPC; Regeneration; Signal Transduction; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; SVZ; myelin; CX3CR1; Regeneration; neural stem cell; chemokine; OPC; fractalkine; SVZ; oligodendrocyte; oligodendrocyte precursor
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2021.06.010

Neural and oligodendrocyte precursor cells (NPCs and OPCs) in the subventricular zone (SVZ) of the brain contribute to oligodendrogenesis throughout life, in part due to direct regulation by chemokines. The role of the chemokine fractalkine is well established in microglia; however, the effect of fractalkine on SVZ precursor cells is unknown. We show that murine SVZ NPCs and OPCs express the fractalkine receptor (CX3CR1) and bind fractalkine. Exogenous fractalkine directly enhances OPC and oligodendrocyte genesis from SVZ NPCs in vitro. Infusion of fractalkine into the lateral ventricle of adult NPC lineage-tracing mice leads to increased newborn OPC and oligodendrocyte formation in vivo. We also show that OPCs secrete fractalkine and that inhibition of endogenous fractalkine signaling reduces oligodendrocyte formation in vitro. Finally, we show that fractalkine signaling regulates oligodendrogenesis in cerebellar slices ex vivo. In summary, we demonstrate a novel role for fractalkine signaling in regulating oligodendrocyte genesis from postnatal CNS precursor cells. [Display omitted] •Postnatal and adult murine SVZ precursor cells express Cx3cr1 and bind fractalkine•Fractalkine enhances OPC and oligodendrocyte formation from SVZ NPCs•Inhibition of fractalkine signaling reduces SVZ NPC and OPC oligodendrogenesis•Fractalkine signaling regulates oligodendrogenesis in ex vivo cerebellar slices Watson et al. demonstrate that murine SVZ NPCs and OPCs express Cx3cr1 and bind fractalkine. Exogenous fractalkine increases oligodendrogenesis from SVZ NPCs and OPCs. They also show that OPCs secrete fractalkine and that inhibition of endogenous fractalkine signaling reduces SVZ oligodendrocyte formation. Finally, they show that fractalkine signaling is an important regulator of oligodendrocyte genesis in other brain areas, such as the cerebellum.