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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Elsevier B.V.
Abstract
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
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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, Physiology