Ciliary abnormalities in senescent human fibroblasts impair proliferative capacity
Open accessAbstract
Somatic cells senesce in culture after a finite number of divisions indefinitely arresting their proliferation. DNA damage and senescence increase the cellular number of centrosomes, the 2 microtubule organizing centers that ensure bipolar mitotic spindles. Centrosomes also provide the basal body from which primary cilia extend to sense and transduce various extracellular signals, notably Hedgehog. Primary cilium formation is facilitated by cellular quiescence a temporary cell cycle exit, but the impact of senescence on cilia is unknown. We found that senescent human fibroblasts have increased frequency and length of primary cilia. Levels of the negative ciliary regulator CP110 were reduced in senescent cells, as were levels of key elements of the Hedgehog pathway. Hedgehog inhibition reduced proliferation in young cells with increased cilium length accompanying cell cycle arrest suggesting a regulatory function for Hedgehog in primary ciliation. Depletion of CP110 in young cell populations increased ciliation frequencies and reduced cell proliferation. These data suggest that primary cilia are potentially novel determinants of the reduced cellular proliferation that initiates senescence.
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The core signature includes BCL2L2, PATZ1, and SMO, genes previously linked to senescence.
“Nevertheless, within the senescence core signature, we found genes that had been previously linked to senescence: BCL2L2 (also known as Bcl-w), a negative regulator of apoptosis [26]; PATZ1, a transcriptional repressor whose expression inhibits senescence in endothelial cells [27]; SMO, a component of the Hedgehog pathway [28]; and CCND1, a regulatory subunit of CDK4 or CDK6, whose activity is req”
From Unmasking Transcriptional Heterogeneity in Senescent Cells (2017) · cites this paper as [28]
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- Authors
- Breslin, L., Prosser, S. L., Cuffe, S., & Morrison, C. G.
- Affiliations
- Ollscoil na Gaillimhe – University of Galway (IE)
- Corresponding author
- Morrison, Ciaran G
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2014-09-02
- Volume
- 13
- Issue
- 17
- Pages
- 2773-2779
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC4613152
- OpenAlex
- W2051054464
- Cited by
- 39
- References
- 42
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 1 · 2014: 1
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc-nd)
- Figshare (submittedVersion, cc-by)
- Figshare (cc-by)
- Funders
- Irish Cancer Society
- Science Foundation Ireland (10/IN.1/B2972)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- cellular senescence, primary cilia, ciliary abnormalities, fibroblasts, cell proliferation, Hedgehog signaling, CP110, centrosome, ciliation, cell cycle arrest, DNA damage
- MeSH terms
- Cells, Cultured, Cilia, Fibroblasts, Humans, Microtubule-Associated Proteins, Phosphoproteins, Cellular Senescence, Cell Cycle Proteins, Cell Proliferation, Hedgehog Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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