MHC class I H2-Kb negatively regulates neural progenitor cell proliferation by inhibiting FGFR signaling

Author:

Lin Karin,Bieri GregorORCID,Gontier GeraldineORCID,Müller Sören,Smith Lucas K.ORCID,Snethlage Cedric E.,White Charles W.,Maybury-Lewis Sun Y.ORCID,Villeda Saul A.ORCID

Abstract

Proteins of the major histocompatibility complex class I (MHC I), predominantly known for antigen presentation in the immune system, have recently been shown to be necessary for developmental neural refinement and adult synaptic plasticity. However, their roles in nonneuronal cell populations in the brain remain largely unexplored. Here, we identify classical MHC I molecule H2-Kb as a negative regulator of proliferation in neural stem and progenitor cells (NSPCs). Using genetic knockout mouse models and in vivo viral-mediated RNA interference (RNAi) and overexpression, we delineate a role for H2-Kb in negatively regulating NSPC proliferation and adult hippocampal neurogenesis. Transcriptomic analysis of H2-Kb knockout NSPCs, in combination with in vitro RNAi, overexpression, and pharmacological approaches, further revealed that H2-Kb inhibits cell proliferation by dampening signaling pathways downstream of fibroblast growth factor receptor 1 (Fgfr1). These findings identify H2-Kb as a critical regulator of cell proliferation through the modulation of growth factor signaling.

Funder

California Institute for Regenerative Medicine

Hillblom Foundation

ARCS Foundation

Glenn Foundation

National Institute on Aging

Publisher

Public Library of Science (PLoS)

Subject

General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience

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