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

First Author  Lin K Year  2021
Journal  PLoS Biol Volume  19
Issue  6 Pages  e3001311
PubMed ID  34181639 Mgi Jnum  J:326348
Mgi Id  MGI:6726216 Doi  10.1371/journal.pbio.3001311
Citation  Lin K, et al. (2021) MHC class I H2-Kb negatively regulates neural progenitor cell proliferation by inhibiting FGFR signaling. PLoS Biol 19(6):e3001311
abstractText  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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