Sentinel p16 INK4a+ cells in the basement membrane form a reparative niche in the lung
Open accessAbstract
We engineered an ultrasensitive reporter of p16 INK4a , a biomarker of cellular senescence. Our reporter detected p16 INK4a -expressing fibroblasts with certain senescent characteristics that appeared shortly after birth in the basement membrane adjacent to epithelial stem cells in the lung. Furthermore, these p16 INK4a+ fibroblasts had enhanced capacity to sense tissue inflammation and respond through their increased secretory capacity to promote epithelial regeneration. In addition, p16 INK4a expression was required in fibroblasts to enhance epithelial regeneration. This study highlights a role for p16 INK4a+ fibroblasts as tissue-resident sentinels in the stem cell niche that monitor barrier integrity and rapidly respond to inflammation to promote tissue regeneration.
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Senescent cells have important physiological roles and their clearance may be detrimental in certain conditions.
“It should be noted, however, that senescent cells also have important physiological roles and that their clearance may be detrimental in certain conditions3–5.”
From Spatial mapping of cellular senescence: emerging challenges and opportunities (2023) · cites this paper as [5]
There are beneficial effects of senescent cells in certain circumstances.
“Furthermore, there are beneficial effects of senescent cells in certain circumstances, which brings more critical requirements to study the right time and condition for senolytics to overcome the harmful effects.16”
From Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators (2024) · cites this paper as [16]
Cellular senescence is not a mammalian-specific phenomenon but is widespread across the animal kingdom, including vertebrate and invertebrate organisms.
“Cellular senescence is not a mammalian-specific phenomenon but is widespread across the animal kingdom, including vertebrate and invertebrate organisms.”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [116]
The Abstract and Discussion describe p16INK4a-expressing cells and senescent characteristics in mice, but do not address whether cellular senescence occurs across the animal kingdom. Searches for vertebrates, invertebrates, and evolutionary conservation found no passage supporting that claim; page numbers are unavailable in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredSenescence in non-mammals impacts many aspects of organismal physiology, from development to regeneration and ageing.
“Senescence in non-mammals impacts on many aspects of organismal physiology, from development116,122 to regeneration (e.g., salamander limbs117, zebrafish fins118, whole hydra polyps120) and ageing119,123,124.”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [116]
Citation 117 is attached to the example of salamander limb regeneration. The paper’s Abstract and section on epithelial stem cell regeneration describe lung repair in mice, not salamanders or other non-mammals. Searches for salamanders, axolotls, limbs, zebrafish and hydra found no passage addressing that example. (LLM, conf=0.76)
Experimental — accuracy not yet measuredMarkers of senescence have been detected in birds, amphibians, fish, and invertebrates.
“Markers of senescence have been detected in birds (e.g., quail114), amphibians (e.g., axolotls115, xenopus116, and newts117), fish (e.g., zebrafish118 and killifish119), and invertebrates (e.g., hydra120 and Drosophila121).”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [116]
The 'High-sensitivity fluorescent reporter of p16 INK4a in vivo' section (page unavailable) reports senescence markers in mouse lung fibroblasts, not in any of the animal groups named in the claim. Searches for the named species and for senescence markers in non-mammalian animals found no passage addressing those groups. (LLM, conf=0.76)
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Self-citation
- Authors
- Reyes, N. S., Krasilnikov, M., Allen, N. C., Lee, J. Y., Hyams, B., Zhou, M., Ravishankar, S., Cassandras, M., Wang, C., Khan, I., Matatia, P., Johmura, Y., Molofsky, A., Matthay, M., Nakanishi, M., Sheppard, D., Campisi, J., & Peng, T.
- Affiliations
- University of California, San Francisco (US)
- The University of Tokyo (JP)
- Buck Institute for Research on Aging (US)
- Corresponding author
- Peng, Tien
- ORCID
- Venue
- Science
- Published
- 2022-10-14
- Volume
- 378
- Issue
- 6616
- Pages
- 192-201
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC10621323
- OpenAlex
- W4305040316
- Cited by
- 181
- References
- 38
- Citations by year
- 2026: 45 · 2025: 40 · 2024: 54 · 2023: 34 · 2022: 4 · 2021: 2 · 2020: 2
- FWCI
- 20.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Tobacco-Related Disease Research Program
- National Institutes of Health (DK063720)
- Japan Society for the Promotion of Science (20H00514, 19H03431)
- National Institute on Aging (DP2AG056034)
- National Heart, Lung, and Blood Institute (R01HL155622, R01HL142552, R01HL160895)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063720)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Keywords
- p16INK4a, cellular senescence, epithelial stem cells, stem cell niche, tissue regeneration, secretory capacity, reporter system
- MeSH terms
- Basement Membrane, Epithelial Cells, Fibroblasts, Humans, Inflammation, Lung, Regeneration, Biomarkers, Cellular Senescence, Genes, Reporter, Cyclin-Dependent Kinase Inhibitor p16, Stem Cell Niche
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