The DOI matches its Crossref record; 97 of the 98 references it cites were found in a registry or an index.
Generation of a p16 Reporter Mouse and Its Use to Characterize and Target p16high Cells In Vivo
Open accessAbstract
Cell senescence plays a key role in age-associated organ dysfunction, but the in vivo pathogenesis is largely unclear. Here, we generated a p16-Cre ERT2-tdTomato mouse model to analyze the in vivo characteristics of p16 high cells at a single-cell level. We found tdTomato-positive p16 high cells detectable in all organs, which were enriched with age. We also found that these cells failed to proliferate and had half-lives ranging from 2.6 to 4.2 months, depending on the tissue examined. Single-cell transcriptomics in the liver and kidneys revealed that p16 high cells were present in various cell types, though most dominant in hepatic endothelium and in renal proximal and distal tubule epithelia, and that these cells exhibited heterogeneous senescence-associated phenotypes. Further, elimination of p16 high cells ameliorated nonalcoholic steatohepatitis-related hepatic lipidosis and immune cell infiltration. Our new mouse model and single-cell analysis provide a powerful resource to enable the discovery of previously unidentified senescence functions in vivo.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Citations
Cites
SCANPY: large-scale single-cell gene expression data analysis
Wolf, F. A., Angerer, P., & Theis, F. J. (2018) · Genome Biology · doi:10.1186/s13059-017-1382-0 · Cited by 8,881
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction
McInnes, L., Healy, J., & Melville, J. (2018) · arXiv · doi:10.48550/arxiv.1802.03426 · Cited by 7,101
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
The Ki-67 protein: From the known and the unknown
Scholzen, T. E., & Gerdes, J. (2000) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(200003)182:3 · Cited by 4,707
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
Cellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225
Jacomy, M., Venturini, T., Heymann, S., & Bastian, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098679 · Cited by 2,909
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
Cited by
Sorted by citations
Exploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867
Senescence and cancer — role and therapeutic opportunities
Schmitt, C. A., Wang, B., & Demaria, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00668-4 · Cited by 794
Cellular senescence: a key therapeutic target in aging and diseases
Zhang, L., Pitcher, L. E., Yousefzadeh, M. J., Niedernhofer, L. J., Robbins, P. D., & Zhu, Y. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158450 · Cited by 631
“The use of p16Ink4a-high senescent cell reporter mice (p16LUC and p16-CreERT2-tdTomato mice) revealed that p16Ink4a-expressing SnCs progressively increased with age and drove aging and cancer processes in mice (18, 46, 47).”
BackgroundStrategies for targeting senescent cells in human disease
Gasek, N. S., Kuchel, G. A., Kirkland, J. L., & Xu, M. (2021) · Nature Aging · doi:10.1038/s43587-021-00121-8 · Cited by 501
Blocking PD-L1–PD-1 improves senescence surveillance and ageing phenotypes
Wang, T.-W., Johmura, Y., Suzuki, N., Omori, S., Migita, T., Yamaguchi, K., Hatakeyama, S., Yamazaki, S., Shimizu, E., Imoto, S., et al. (2022) · Nature · doi:10.1038/s41586-022-05388-4 · Cited by 469
Self-citation
Metadata
- Authors
- Omori, S., Wang, T.-W., Johmura, Y., Kanai, T., Nakano, Y., Kido, T., Susaki, E. A., Nakajima, T., Shichino, S., Ueha, S., Ozawa, M., Yokote, K., Kumamoto, S., Nishiyama, A., Sakamoto, T., Yamaguchi, K., Hatakeyama, S., Shimizu, E., Katayama, K., Yamada, Y., Yamazaki, S., Iwasaki, K., Miyoshi, C., Funato, H., Yanagisawa, M., Ueno, H., Imoto, S., Furukawa, Y., Yoshida, N., Matsushima, K., Ueda, H. R., Miyajima, A., & Nakanishi, M.
- Affiliations
- Institute of Medical Science, The University of Tokyo (JP)
- Institute for Quantitative Biosciences, The University of Tokyo (JP)
- RIKEN Center for Biosystems Dynamics Research (JP)
- Tokyo University of Science (JP)
- Kanazawa University (JP)
- Japan Agency for Medical Research and Development (JP)
- University of Tsukuba (JP)
- Toho University (JP)
- Kansai Medical University (JP)
- Corresponding author
- Johmura, Yoshikazu
- Nakanishi, Makoto
- ORCID
- Omori, Satotaka
- Wang, Teh-Wei
- Johmura, Yoshikazu
- Kanai, Tomomi
- Nakano, Yasuhiro
- Kido, Taketomo
- Susaki, Etsuo A.
- Shichino, Shigeyuki
- Ueha, Satoshi
- Ozawa, Manabu
- Kumamoto, Soichiro
- Nishiyama, Atsuya
- Sakamoto, Takeharu
- Yamaguchi, Kiyoshi
- Hatakeyama, Seira
- Shimizu, Eigo
- Katayama, Kotoe
- Yamada, Yasuhiro
- Yamazaki, Satoshi
- Miyoshi, Chika
- Funato, Hiromasa
- Yanagisawa, Masashi
- Imoto, Seiya
- Furukawa, Yoichi
- Yoshida, Nobuaki
- Matsushima, Kouji
- Ueda, Hiroki R.
- Miyajima, Atsushi
- Nakanishi, Makoto
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 32
- Issue
- 5
- Pages
- 814-828.e6
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W3087571995
- Cited by
- 194
- References
- 98
- Citations by year
- 2026: 30 · 2025: 32 · 2024: 43 · 2023: 37 · 2022: 26 · 2021: 23 · 2020: 3
- FWCI
- 13.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Princess Takamatsu Cancer Research Fund (17H06095, 19H03413, JP16H06276, JP18H05026m, JP19H03431, JP20H04940)
- Ministry of Education, Culture, Sports, Science and Technology
- Core Research for Evolutional Science and Technology (A3A28043, AMED JP20am0401411)
- Ono Medical Research Foundation
- Olympus
- Japan Society for the Promotion of Science (JP16K15239, JP17cm0106122, JP17fk0310111, JP17gm5010001, JP20ck0106550, JP22118003, JP26250027)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, nonalcoholic steatohepatitis, hepatic lipidosis, immune cell infiltration, single-cell analysis
- MeSH terms
- Animals, Cell Line, Humans, Mice, Inbred C57BL, Models, Biological, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Mice, Single-Cell Analysis
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 ›
Are you an author, or do you see a problem with this page? Request a review
