The Rb/E2F axis is a key regulator of the molecular signatures instructing the quiescent and activated adult neural stem cell state
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24 janvier 2025
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Cell Reports
Mots-clés
Activation Adult neurogenesis Cell fate Cp: neuroscience Cp: stem cell research Molecular signature Neural precursors Neural stem cells Quiescence Rb/e2f pathway Stem cell maintenance Transcriptional regulation Adult stem cells Cell cycle Cell division Neurogenesis Retinoblastoma protein Doublecortin like kinase Ki 67 antigen Transcription factor e2f1 Transcription factor mash1 Transcription factor sox2 A-549 cell line Adult Animal cell Animal experiment Animal model Animal tissue Article Bioinformatics Cell cycle regulation Cell differentiation Cell proliferation Chromatin immunoprecipitation Controlled study Differential gene expression Down regulation Expression vector Flow cytometry Fluorescence activated cell sorting Gene expression Gene mutation Hct 116 cell line Hek293 cell line Hek293t cell line Hela s3 cell line Hep-g2 cell line High throughput sequencing Hl-60 cell line Human Human cell Immunohistochemistry Immunoprecipitation K-562 cell line Mcf-7 cell line Mouse Nerve cell differentiation Nervous system development Neural stem cell Nonhuman Panc-1 cell line Polyacrylamide gel electrophoresis Protein expression Real time polymerase chain reaction Rna isolation Sk-n-sh cell line Tissue perfusion Transcriptomics Upregulation Western blotting Adult stem cell Genetics Metabolism PhysiologySujets proches
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Fong et al., « The Rb/E2F axis is a key regulator of the molecular signatures instructing the quiescent and activated adult neural stem cell state », American University of Beirut ScholarWorks
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Résumé
Long-term maintenance of the adult neurogenic niche depends on proper regulation of entry and exit from quiescence. Neural stem cell (NSC) transition from quiescence to activation is a complex process requiring precise cell-cycle control coordinated with transcriptional and morphological changes. How NSC fate transitions in coordination with the cell-cycle machinery remains poorly understood. Here we show that the Rb/E2F axis functions by linking the cell-cycle machinery to pivotal regulators of NSC fate. Deletion of Rb family proteins results in activation of NSCs, inducing a transcriptomic transition toward activation. Deletion of their target activator E2Fs1/3 results in intractable quiescence and cessation of neurogenesis. We show that the Rb/E2F axis mediates these fate transitions through regulation of factors essential for NSC function, including REST and ASCL1. Thus, the Rb/E2F axis is an important regulator of NSC fate, coordinating cell-cycle control with NSC activation and quiescence fate transitions. © 2022 The Authors
