ArticleProceedings of the National Academy of Sciences of the United States of America2019
Graded regulation of cellular quiescence depth between proliferation and senescence by a lysosomal dimmer switch.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- "Quiescence" in the resting zone of the growth plate: a systematic review.Stem cells (Dayton, Ohio) · 2026Pooled it
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- HLH-30/TFEB is necessary for chromatin reorganization and maintenance of cell quiescence during starvation in C. elegans.Nucleic acids research · 2026Article
- Increased mRNA translation delays tumour initiation and exposes a therapeutic vulnerability in lung cancer.Molecular cancer · 2026Article
- 3D Soft Hydrogels Induce Human Mesenchymal Stem Cells "Deep" Quiescence.Advanced healthcare materials · 2026Article
- Computational Approaches to Cancer Cell Dormancy: From Detection to Dynamic Modelling.Biomolecules · 2026Review
- New Insights into the Anti-Aging Mechanism of Collagen Peptides-Emphasis on Lysosomes and Mitochondria Function.Molecules (Basel, Switzerland) · 2026Review
- Elevated endocytic trafficking mediated by GPRASP2 maintains HSC fidelity.bioRxiv : the preprint server for biology · 2026Article
- The dual role of autophagy in cartilage degradation: from mechanisms to targeted therapeutics.Frontiers in cell and developmental biology · 2026Review
- Single-cell RNA sequencing reveals a quiescence-senescence continuum and distinct senotypes following chemotherapy.Nature communications · 2025Article
- Prolonged starvation deepens quiescence in Vasa2/Piwi1-expressing cells of a sea anemone.PLoS biology · 2025Article
- Decoding cancer dormancy: integrative genomic, phenotypic and live-cell imaging analysis to reveal the hidden cancer cell reservoir.Molecular cancer · 2025Review
- Lysosomal and mTORC1 signaling dysregulation underpin the pathology of spastic paraplegia type 80.Nature communications · 2025Article
- Quiescence Multiverse.Biomolecules · 2025Review
- Epigenetic regulation of neural stem cell aging in the mouse hippocampus by Setd8 downregulation.The EMBO journal · 2025Article
- Reversible proliferative arrest induced by rapid depletion of RNase MRP.Nature communications · 2025Article
- Sequential transcriptional programs underpin activation of hippocampal stem cells.Science advances · 2025Article
- Selection and validation of reference genes for RT-qPCR normalization in dormant cancer cells.Scientific reports · 2025Article
- Same same but different? How blood and lymphatic vessels induce cell contact inhibition.Biochemical Society transactions · 2025Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The reactivation of quiescent cells to proliferate is fundamental to tissue repair and homeostasis in the body. Often referred to as the G0 state, quiescence is, however, not a uniform state but with graded depth. Shallow quiescent cells exhibit a higher tendency to revert to proliferation than deep quiescent cells, while deep quiescent cells are still fully reversible under physiological conditions, distinct from senescent cells. Cellular mechanisms underlying the control of quiescence depth and the connection between quiescence and senescence are poorly characterized, representing a missing link in our understanding of tissue homeostasis and regeneration. Here we measured transcriptome changes as rat embryonic fibroblasts moved from shallow to deep quiescence over time in the absence of growth signals. We found that lysosomal gene expression was significantly up-regulated in deep quiescence, and partially compensated for gradually reduced autophagy flux. Reducing lysosomal function drove cells progressively deeper into quiescence and eventually into a senescence-like irreversibly arrested state; increasing lysosomal function, by lowering oxidative stress, progressively pushed cells into shallower quiescence. That is, lysosomal function modulates graded quiescence depth between proliferation and senescence as a dimmer switch. Finally, we found that a gene-expression signature developed by comparing deep and shallow quiescence in fibroblasts can correctly classify a wide array of senescent and aging cell types in vitro and in vivo, suggesting that while quiescence is generally considered to protect cells from irreversible arrest of senescence, quiescence deepening likely represents a common transition path from cell proliferation to senescence, related to aging.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.