The Rb/E2F axis is a key regulator of the molecular signatures instructing the quiescent and activated adult neural stem cell state

Ajioka, 2007, Differentiated horizontal interneurons clonally expand to form metastatic retinoblastoma in mice, Cell, 131, 378, 10.1016/j.cell.2007.09.036 Andersen, 2014, A transcriptional mechanism integrating inputs from extracellular signals to activate hippocampal stem cells, Neuron, 83, 1085, 10.1016/j.neuron.2014.08.004 Andrews, 2012 Ballas, 2005, REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis, Cell, 121, 645, 10.1016/j.cell.2005.03.013 Basak, 2018, Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy, Proc. Natl. Acad. Sci. USA, 115, E610, 10.1073/pnas.1715911114 Bergsland, 2006, The establishment of neuronal properties is controlled by Sox4 and Sox11, Genes Dev., 20, 3475, 10.1101/gad.403406 Burkhart, 2010, Regulation of RB transcription in vivo by RB family members, Mol. Cell Biol., 30, 1729, 10.1128/MCB.00952-09 Callaghan, 1999, Neural precursor cells differentiating in the absence of Rb exhibit delayed terminal mitosis and deregulated E2F 1 and 3 activity, Dev. Biol., 207, 257, 10.1006/dbio.1998.9162 Chen, 2009, Division and apoptosis of E2f-deficient retinal progenitors, Nature, 462, 925, 10.1038/nature08544 Chen, 1998, NRSF/REST is required in vivo for repression of multiple neuronal target genes during embryogenesis, Nat. Genet., 20, 136, 10.1038/2431 Chong, 1995, REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons, Cell, 80, 949, 10.1016/0092-8674(95)90298-8 Chong, 2009, E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells, Nature, 462, 930, 10.1038/nature08677 Cicero, 2009, Cells previously identified as retinal stem cells are pigmented ciliary epithelial cells, Proc. Natl. Acad. Sci. USA, 106, 6685, 10.1073/pnas.0901596106 Codega, 2014, Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche, Neuron, 82, 545, 10.1016/j.neuron.2014.02.039 Cooper-Kuhn, 2002, Impaired adult neurogenesis in mice lacking the transcription factor E2F1, Mol. Cell. Neurosci., 21, 312, 10.1006/mcne.2002.1176 Davis, 2018, The Encyclopedia of DNA elements (ENCODE): data portal update, Nucleic Acids Res., 46, D794, 10.1093/nar/gkx1081 Delgado, 2021, Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brain, Science, 372, 1205, 10.1126/science.abg8467 Dunham, 2012, An integrated encyclopedia of DNA elements in the human genome, Nature, 489, 57, 10.1038/nature11247 Durinck, 2009, Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt, Nat. Protoc., 4, 1184, 10.1038/nprot.2009.97 Encinas, 2011, Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult Hippocampus, Cell Stem Cell, 8, 566, 10.1016/j.stem.2011.03.010 Ferland, 2009, Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia, Hum. Mol. Genet., 18, 497, 10.1093/hmg/ddn377 Field, 1996, E2F-1 functions in mice to promote apoptosis and suppress proliferation, Cell, 85, 549, 10.1016/S0092-8674(00)81255-6 Friend, 1986, A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma, Nature, 323, 643, 10.1038/323643a0 Gao, 2011, The master negative regulator REST/NRSF controls adult neurogenesis by restraining the neurogenic program in quiescent stem cells, J. Neurosci., 31, 9772, 10.1523/JNEUROSCI.1604-11.2011 Gonçalves, 2016, Adult neurogenesis in the Hippocampus: from stem cells to behavior, Cell, 167, 897, 10.1016/j.cell.2016.10.021 Hodge, 2012, Tbr2 is essential for hippocampal lineage progression from neural stem cells to intermediate progenitors and neurons, J. Neurosci., 32, 6275, 10.1523/JNEUROSCI.0532-12.2012 Ignatiadis, 2016, Data-driven hypothesis weighting increases detection power in genome-scale multiple testing, Nat. Methods, 13, 577, 10.1038/nmeth.3885 Iqbal, 2022, Direct FACS isolation of neural stem/progenitor lineages from the adult brain, Methods Mol. Biol., 2515, 117, 10.1007/978-1-0716-2409-8_8 Jaafar, 2016, Role of Rb during neurogenesis and axonal guidance in the developing olfactory system, Front. Mol. Neurosci., 9, 81, 10.3389/fnmol.2016.00081 Janky, 2014, iRegulon: from a gene list to a gene regulatory network using large motif and track collections, PLoS Comput. Biol., 10, 10037311, 10.1371/journal.pcbi.1003731 Jiang, 2010, Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status, J. Clin. Invest., 120, 3296, 10.1172/JCI41490 Jørgensen, 2009, REST selectively represses a subset of RE1-containing neuronal genes in mouse embryonic stem cells, Development, 136, 715, 10.1242/dev.028548 Julian, 2016, Tissue-specific targeting of cell fate regulatory genes by E2f factors, Cell Death Differ., 23, 565, 10.1038/cdd.2015.36 Julian, 2013, Opposing regulation of Sox2 by cell-cycle effectors E2f3a and E2f3b in neural stem cells, Cell Stem Cell, 12, 440, 10.1016/j.stem.2013.02.001 Kareta, 2015, Inhibition of pluripotency networks by the Rb tumor suppressor restricts reprogramming and tumorigenesis, Cell Stem Cell, 16, 39, 10.1016/j.stem.2014.10.019 Kim, 2019, Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype, Nat. Biotechnol., 37, 907, 10.1038/s41587-019-0201-4 Kim, 2017, Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression, J. Exp. Med., 214, 1901, 10.1084/jem.20160719 Kwon, 2017, Controlling depth of cellular quiescence by an Rb-E2F network switch, Cell Rep., 20, 3223, 10.1016/j.celrep.2017.09.007 Lee, 1987, The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity, Nature, 329, 642, 10.1038/329642a0 Lepagnol-Bestel, 2009, DYRK1A interacts with the REST/NRSF-SWI/SNF chromatin remodelling complex to deregulate gene clusters involved in the neuronal phenotypic traits of Down syndrome, Hum. Mol. Genet., 18, 1405, 10.1093/hmg/ddp047 Liao, 2014, featureCounts: an efficient general purpose program for assigning sequence reads to genomic features, Bioinformatics, 30, 923, 10.1093/bioinformatics/btt656 Litovchick, 2007, Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence, Mol. Cell, 26, 539, 10.1016/j.molcel.2007.04.015 Liu, 2010, Cooperation between myogenic regulatory factors and SIX family transcription factors is important for myoblast differentiation, Nucleic Acids Res., 38, 6857, 10.1093/nar/gkq585 Love, 2014, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2, Genome Biol., 15, 550, 10.1186/s13059-014-0550-8 McClellan, 2007, Unique requirement for Rb/E2F3 in neuronal migration: evidence for cell cycle-independent functions, Mol. Cell Biol., 27, 4825, 10.1128/MCB.02100-06 McGann, 2020, Genome-wide assessment of REST binding profiles reveals distinctions between human and mouse hippocampus, Preprint at bioRxiv Merico, 2010, Enrichment Map: a network-based method for gene-set enrichment visualization and interpretation, PLoS One, 5, e13984, 10.1371/journal.pone.0013984 Miles, 2008, Hypoxic-ischemic brain injury activates early hippocampal stem/progenitor cells to replace vulnerable neuroblasts, Hippocampus, 18, 793, 10.1002/hipo.20439 Morris, 2001, Retinoblastoma protein partners, Adv. Cancer Res., 82, 1, 10.1016/S0065-230X(01)82001-7 Mu, 2012, SoxC transcription factors are required for neuronal differentiation in adult hippocampal neurogenesis, J. Neurosci., 32, 3067, 10.1523/JNEUROSCI.4679-11.2012 Mukherjee, 2016, REST regulation of gene networks in adult neural stem cells, Nat. Commun., 7, 13360, 10.1038/ncomms13360 Naser, 2016, Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb, Sci. Rep., 6, 20230, 10.1038/srep20230 Obernier, 2019, Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain, Development, 146, dev156059, 10.1242/dev.156059 Raudvere, 2019, g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update), Nucleic Acids Res., 47, W191, 10.1093/nar/gkz369 Reimand, 2019, Pathway enrichment analysis and visualization of omics data using g:Profiler, GSEA, Cytoscape and EnrichmentMap, Nat. Protoc., 14, 482, 10.1038/s41596-018-0103-9 Reimand, 2007, g:Profiler—a web-based toolset for functional profiling of gene lists from large-scale experiments, Nucleic Acids Res., 35, W193, 10.1093/nar/gkm226 Reynolds, 1992, Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system, Science (New York, N.Y.), 255, 1707, 10.1126/science.1553558 Robinson, 2011, Integrative genomics viewer, Nat. Biotechnol., 29, 24, 10.1038/nbt.1754 Sage, 2000, Targeted disruption of the three Rb-related genes leads to loss of G1 control and immortalization, Genes Dev., 14, 3037, 10.1101/gad.843200 Sage, 2003, Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry, Nature, 424, 223, 10.1038/nature01764 Schindelin, 2012, Fiji: an open-source platform for biological-image analysis, Nat. Methods, 9, 676, 10.1038/nmeth.2019 Schneider, 2012, NIH Image to ImageJ: 25 years of image analysis, Nat. Methods, 9, 671, 10.1038/nmeth.2089 Schoenherr, 1995, The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes, Science, 267, 1360, 10.1126/science.7871435 Shannon, 2003, Cytoscape: a software environment for integrated models of biomolecular interaction networks, Genome Res., 13, 2498, 10.1101/gr.1239303 Soldati, 2015, RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro, J. Neurosci. Res., 93, 1203, 10.1002/jnr.23572 Srinivas, 2001, Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus, BMC Dev. Biol., 1, 4, 10.1186/1471-213X-1-4 TANG, 2015, Optimization of lentiviral vector production using polyethylenimine-mediated transfection, Oncol. Lett., 9, 55, 10.3892/ol.2014.2684 2021 Urbán, 2016, Return to quiescence of mouse neural stem cells by degradation of a proactivation protein, Science, 353, 292, 10.1126/science.aaf4802 Urbán, 2019, Quiescence of adult mammalian neural stem cells: a highly regulated rest, Neuron, 104, 834, 10.1016/j.neuron.2019.09.026 Vandenbosch, 2016, RB regulates the production and the survival of newborn neurons in the embryonic and adult dentate gyrus, Hippocampus, 26, 1379, 10.1002/hipo.22613 Vanderluit, 2004, p107 regulates neural precursor cells in the mammalian brain, J. Cell Biol., 166, 853, 10.1083/jcb.200403156 Vanderluit, 2007, The Retinoblastoma family member p107 regulates the rate of progenitor commitment to a neuronal fate, J. Cell Biol., 178, 129, 10.1083/jcb.200703176 Viatour, 2011, Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway, J. Exp. Med., 208, 1963, 10.1084/jem.20110198 Viatour, 2008, Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family, Cell Stem Cell, 3, 416, 10.1016/j.stem.2008.07.009 Wang, 2016, Traumatic brain injury stimulates neural stem cell proliferation via mammalian target of rapamycin signaling pathway activation, ENeuro, 3, 10.1523/ENEURO.0162-16.2016 Wu, 2001, The E2F1–3 transcription factors are essential for cellular proliferation, Nature, 414, 457, 10.1038/35106593 Xi, 2016, Knockout of Atg5 delays the maturation and reduces the survival of adult-generated neurons in the hippocampus, Cell Death Dis., 7, e2127, 10.1038/cddis.2015.406 Zhou, 2019, NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis, Nucleic Acids Res., 47, W234, 10.1093/nar/gkz240