Open AccessMHC class I H2-Kb negatively regulates neural progenitor cell proliferation by inhibiting FGFR signaling
Author(s) -
Karin Lin,
Gregor Bieri,
Géraldine Gontier,
Sören Müller,
Lucas K. Smith,
Cedric E Snethlage,
Charles White,
Sun Y. Maybury-Lewis,
Saul Villeda
Publication year - 2021
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001311
Subject(s) - biology , neurogenesis , microbiology and biotechnology , progenitor cell , neural stem cell , cell growth , fibroblast growth factor , rna interference , stem cell , genetics , receptor , rna , gene
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-K b 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-K b in negatively regulating NSPC proliferation and adult hippocampal neurogenesis. Transcriptomic analysis of H2-K b knockout NSPCs, in combination with in vitro RNAi, overexpression, and pharmacological approaches, further revealed that H2-K b inhibits cell proliferation by dampening signaling pathways downstream of fibroblast growth factor receptor 1 (Fgfr1). These findings identify H2-K b as a critical regulator of cell proliferation through the modulation of growth factor signaling.