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

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.

Automated summary

The study revealed that the MHC I class protein H2-K-b plays a crucial role in negatively regulating the proliferation of neural stem and progenitor cells by modulating growth factor signaling pathways, impacting adult hippocampal neurogenesis.