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

PLoS Biology - Tập 19 Số 6 - Trang e3001311
Karin Lin1,2, Gregor Bieri1, Géraldine Gontier1, Sören Müller3, Lucas K. Smith4,1, Cedric E. Snethlage1, Charles White1,5, Sun Kim6, Saul Villeda4,1,7,5,2,8
1Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America.
2Neuroscience Graduate Program, University of California San Francisco, San Francisco, California, United States of America
3Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America
4Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, California, United States of America
5Developmental and Stem Cell Biology Graduate Program, University of California San Francisco, San Francisco, California, United States of America
6Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island, United States of America
7Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, California, United States of America
8The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, San Francisco, California, United States of America

Tóm tắt

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.

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Tập 19 Số 6

e3001311

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