MHC class I H2-Kb negatively regulates neural progenitor cell proliferation by inhibiting FGFR signaling
| Autor: | Charles W. White, Gregor Bieri, Sören Müller, Saul A. Villeda, Sun Y. Maybury-Lewis, Cedric E. Snethlage, Geraldine Gontier, Karin Lin, Lucas K. Smith |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Aging Fibroblast Growth Factor Physiology Gene Expression Fibroblast growth factor Hippocampus Major Histocompatibility Complex Endocrinology 0302 clinical medicine Neural Stem Cells Short Reports Animal Cells Hippocampal Neurogenesis Medicine and Health Sciences Biology (General) Mice Knockout biology Stem Cells General Neuroscience Cell Cycle Neurogenesis Brain Cell Differentiation Animal Models Cell biology Experimental Organism Systems Fibroblast growth factor receptor Anatomy Cellular Types Signal transduction Stem cell General Agricultural and Biological Sciences Neuronal Differentiation Signal Transduction QH301-705.5 Immunology Antigen presentation Mouse Models Research and Analysis Methods General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Model Organisms Developmental Neuroscience Growth Factors MHC class I Genetics Animals Receptor Fibroblast Growth Factor Type 1 Progenitor cell Cell Proliferation Endocrine Physiology General Immunology and Microbiology Histocompatibility Antigens Class I Biology and Life Sciences Cell Biology Mice Inbred C57BL 030104 developmental biology Cellular Neuroscience Animal Studies biology.protein Clinical Immunology Clinical Medicine 030217 neurology & neurosurgery Developmental Biology Neuroscience |
| Zdroj: | PLoS Biology PLoS Biology, Vol 19, Iss 6, p e3001311 (2021) |
| ISSN: | 1545-7885 |
| Popis: | 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. This study identifies a non-canonical role for the classical Major Histocompatibility Complex (MHC) class I molecule H2-Kb as a negative regulator of neural stem and progenitor cell proliferation, independent of its function in the immune system. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|