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ABSTRACT Many of the cells in mammalian tissues are in a reversible quiescent state; they are not dividing, but retain the ability to proliferate in response to extracellular signals.
Quiescence relies on the activities of transcription factors (TFs) that orchestrate the repression of genes that promote proliferation and establish a quiescence-specific gene expression
program. Here we discuss how the coordinated activities of TFs in different quiescent stem cells and differentiated cells maintain reversible cell cycle arrest and establish cell-protective
signalling pathways. We further cover the emerging mechanisms governing the dysregulation of quiescence TF networks with age. We explore how recent developments in single-cell technologies
have enhanced our understanding of quiescence heterogeneity and gene regulatory networks. We further discuss how TFs and their activities are themselves regulated at the RNA, protein and
chromatin levels. Finally, we summarize the challenges associated with defining TF networks in quiescent cells. Access through your institution Buy or subscribe This is a preview of
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* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS REGULATION OF ADULT STEM CELL QUIESCENCE AND ITS
FUNCTIONS IN THE MAINTENANCE OF TISSUE INTEGRITY Article 15 March 2023 AN INTERMEDIATE RB–E2F ACTIVITY STATE SAFEGUARDS PROLIFERATION COMMITMENT Article Open access 26 June 2024 LRIG1 IS A
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supported by: grants to H.A.C. from the National Institute of General Medical Sciences (R01 GM081686 and R01 GM0866465), National Institutes of Health (R01 AR070245, 1R01 CA221296-01A1 and
1R01 AR084245-01) National Cancer Institute (RC1 CA147961-02 and P50 CA092131) and Cancer Research Institute (Clinic and Laboratory Integration Program grant), a Melanoma Research Alliance
Team Science Award, a Melanoma Research Foundation Award, the Department of Defense (W81XWH-22-1-0920), an Iris Cantor Women’s Health Center/University of California, Los Angeles (UCLA)
Clinical and Translational Science Institute National Institutes of Health grant (UL1TR000124), the UCLA Specialized Program of Research Excellence in Prostate Cancer (P50 CA092131), the
David Geffen School of Medicine Metabolism Theme, the University of California Cancer Research Coordinating Committee, Broad Stem Cell Research Center Innovation Awards, Rose Hills
Foundation and Hal Gaba awards from the UCLA Broad Stem Cell Research Center, a Jonsson Comprehensive Cancer Center Seed Grant and Leader’s Vision Awards. H.A.C. was a Milton E. Cassel
scholar of the Rita Allen Foundation. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los
Angeles, CA, USA Mithun Mitra & Hilary A. Coller * Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Mithun
Mitra & Hilary A. Coller * Department of Computer Science, University of California, Los Angeles, Los Angeles, CA, USA Sandra L. Batista * Molecular Biology Institute, University of
California, Los Angeles, Los Angeles, CA, USA Hilary A. Coller Authors * Mithun Mitra View author publications You can also search for this author inPubMed Google Scholar * Sandra L. Batista
View author publications You can also search for this author inPubMed Google Scholar * Hilary A. Coller View author publications You can also search for this author inPubMed Google Scholar
CONTRIBUTIONS M.M. conceived of the idea and design for the manuscript and produced the figures. All of the authors contributed to writing the manuscript. H.A.C. and S.L.B. prepared
Supplementary Tables 1 and 2. M.M. and H.A.C. edited the manuscript. CORRESPONDING AUTHORS Correspondence to Mithun Mitra or Hilary A. Coller. ETHICS DECLARATIONS COMPETING INTERESTS The
authors declare no competing interests. PEER REVIEW PEER REVIEW INFORMATION _Nature Cell Biology_ thanks the anonymous reviewers for their contribution to the peer review of this work.
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publishing agreement and applicable law. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Mitra, M., Batista, S.L. & Coller, H.A. Transcription factor networks in cellular
quiescence. _Nat Cell Biol_ 27, 14–27 (2025). https://doi.org/10.1038/s41556-024-01582-w Download citation * Received: 13 August 2024 * Accepted: 25 November 2024 * Published: 09 January
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