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
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363
Senolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287
Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome
Yoshimoto, S., Loo, T. M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., et al. (2013) · Nature · doi:10.1038/nature12347 · Cited by 2,219
Conditional gene targeting in macrophages and granulocytes using LysMcre mice
Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R., & Förster, I. (1999) · Transgenic Research · doi:10.1023/a:1008942828960 · Cited by 2,098
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819
Senescence in Health and Disease
He, S., & Sharpless, N. E. (2017) · Cell · doi:10.1016/j.cell.2017.05.015 · Cited by 1,766
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708
Wolf, F. A., Hamey, F. K., Plass, M., Solana, J., Dahlin, J. S., Göttgens, B., Rajewsky, N., Simon, L., & Theis, F. J. (2019) · Genome Biology · doi:10.1186/s13059-019-1663-x · Cited by 1,698
mTOR is a key modulator of ageing and age-related disease
Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013) · Nature · doi:10.1038/nature11861 · Cited by 1,676
Kang, H. M., Ahn, S. H., Choi, P., Ko, Y.-A., Han, S. H., Chinga, F., Park, A. S. D., Tao, J., Sharma, K., Pullman, J., et al. (2015) · Nature Medicine · doi:10.1038/nm.3762 · Cited by 1,555
Ouelle, D. E., Zindy, F., Ashmun, R. A., & Sherr, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90214-7 · Cited by 1,485
Baar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., Stryeck, S., Rijksen, Y., van Willigenburg, H., Feijtel, D. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.031 · Cited by 1,454
Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis
Susaki, E. A., Tainaka, K., Perrin, D., Kishino, F., Tawara, T., Watanabe, T. M., Yokoyama, C., Onoe, H., Eguchi, M., Yamaguchi, S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.042 · Cited by 1,352
Self-citationL1 drives IFN in senescent cells and promotes age-associated inflammation
De Cecco, M., Ito, T., Petrashen, A. P., Elias, A. E., Skvir, N. J., Criscione, S. W., Caligiana, A., Brocculi, G., Adney, E. M., Boeke, J. D., et al. (2019) · Nature · doi:10.1038/s41586-018-0784-9 · Cited by 1,255
A single-cell transcriptomic atlas characterizes ageing tissues in the mouse
The Tabula Muris Consortium, Almanzar, N., Antony, J., Baghel, A. S., Bakerman, I., Bansal, I., Barres, B. A., Beachy, P. A., Berdnik, D., Bilen, B., et al. (2020) · Nature · doi:10.1038/s41586-020-2496-1 · Cited by 1,247
Computational and analytical challenges in single-cell transcriptomics
Stegle, O., Teichmann, S. A., & Marioni, J. C. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3833 · Cited by 1,170
Forging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104
Fat tissue, aging, and cellular senescence
Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00608.x · Cited by 1,094
Cellular senescence drives age-dependent hepatic steatosis
Ogrodnik, M., Miwa, S., Tchkonia, T., Tiniakos, D., Wilson, C. L., Lahat, A., Day, C. P., Burt, A., Palmer, A., Anstee, Q. M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15691 · Cited by 1,044
Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL
Yosef, R., Pilpel, N., Tokarsky-Amiel, R., Biran, A., Ovadya, Y., Cohen, S., Vadai, E., Dassa, L., Shahar, E., Condiotti, R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11190 · Cited by 1,032
The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Kazankov, K., Jørgensen, S. M. D., Thomsen, K. L., Møller, H. J., Vilstrup, H., George, J., Schuppan, D., & Grønbæk, H. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0082-x · Cited by 941
A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration
Buch, T., Heppner, F. L., Tertilt, C., Heinen, T. J. A. J., Kremer, M., Wunderlich, F. T., Jung, S., & Waisman, A. (2005) · Nature Methods · doi:10.1038/nmeth762 · Cited by 922
A crucial role for adipose tissue p53 in the regulation of insulin resistance
Minamino, T., Orimo, M., Shimizu, I., Kunieda, T., Yokoyama, M., Ito, T., Nojima, A., Nabetani, A., Oike, Y., Matsubara, H., et al. (2009) · Nature Medicine · doi:10.1038/nm.2014 · Cited by 891
Xiong, X., Kuang, H., Ansari, S., Liu, T., Gong, J., Wang, S., Zhao, X.-Y., Ji, Y., Li, C., Guo, L., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.028 · Cited by 784
Non-Cell-Autonomous Tumor Suppression by p53
Lujambio, A., Akkari, L., Simon, J., Grace, D., Tschaharganeh, D. F., Bolden, J. E., Zhao, Z., Thapar, V., Joyce, J. A., Krizhanovsky, V., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.020 · Cited by 766
Wolf, M. J., Adili, A., Piotrowitz, K., Abdullah, Z., Boege, Y., Stemmer, K., Ringelhan, M., Simonavicius, N., Egger, M., Wohlleber, D., et al. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.09.003 · Cited by 678
SuperTarget and Matador: resources for exploring drug-target relationships
Gunther, S., Kuhn, M., Dunkel, M., Campillos, M., Senger, C., Petsalaki, E., Ahmed, J., Urdiales, E. G., Gewiess, A., Jensen, L. J., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm862 · Cited by 647
A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence
Kaplon, J., Zheng, L., Meissl, K., Chaneton, B., Selivanov, V. A., Mackay, G., van der Burg, S. H., Verdegaal, E. M. E., Cascante, M., Shlomi, T., et al. (2013) · Nature · doi:10.1038/nature12154 · Cited by 633
Bonnardel, J., T’Jonck, W., Gaublomme, D., Browaeys, R., Scott, C. L., Martens, L., Vanneste, B., De Prijck, S., Nedospasov, S. A., Kremer, A., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.08.017 · Cited by 631
Solana, R., Tarazona, R., Gayoso, I., Lesur, O., Dupuis, G., & Fulop, T. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.008 · Cited by 567
Replicative Senescence: Implications for in Vivo Aging and Tumor Suppression
Smith, J. R., & Pereira-Smith, O. M. (1996) · Science · doi:10.1126/science.273.5271.63 · Cited by 547
Vascular Cell Senescence: Contribution to Atherosclerosis
Minamino, T., & Komuro, I. (2007) · Circulation Research · doi:10.1161/01.res.0000256837.40544.4a · Cited by 542
Design and Analysis of Single-Cell Sequencing Experiments
Grün, D., & van Oudenaarden, A. (2015) · Cell · doi:10.1016/j.cell.2015.10.039 · Cited by 536
An improved mouse model that rapidly develops fibrosis in non‐alcoholic steatohepatitis
Matsumoto, M., Hada, N., Sakamaki, Y., Uno, A., Shiga, T., Tanaka, C., Ito, T., Katsume, A., & Sudoh, M. (2013) · International Journal of Experimental Pathology · doi:10.1111/iep.12008 · Cited by 523
Acceleration of β Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes
Aguayo-Mazzucato, C., Andle, J., Lee, T. B., Midha, A., Talemal, L., Chipashvili, V., Hollister-Lock, J., van Deursen, J., Weir, G., & Bonner-Weir, S. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.006 · Cited by 469
Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan
Grosse, L., Wagner, N., Emelyanov, A., Molina, C., Lacas-Gervais, S., Wagner, K.-D., & Bulavin, D. V. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.05.002 · Cited by 460
Single-Cell Profiling Reveals Sex, Lineage, and Regional Diversity in the Mouse Kidney
Ransick, A., Lindström, N. O., Liu, J., Zhu, Q., Guo, J., Alvarado, G. F., Kim, A. D., Black, H. G., Kim, J., & McMahon, A. P. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.10.005 · Cited by 431
Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model
Burd, C. E., Sorrentino, J. A., Clark, K. S., Darr, D. B., Krishnamurthy, J., Deal, A. M., Bardeesy, N., Castrillon, D. H., Beach, D. H., & Sharpless, N. E. (2013) · Cell · doi:10.1016/j.cell.2012.12.010 · Cited by 419
Single-Cell Transcriptomics Meets Lineage Tracing
Kester, L., & van Oudenaarden, A. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.04.014 · Cited by 375
Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents
Tainaka, K., Murakami, T. C., Susaki, E. A., Shimizu, C., Saito, R., Takahashi, K., Hayashi‐Takagi, A., Sekiya, H., Arima, Y., Nojima, S., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.056 · Cited by 342
Self-citationCells exhibiting strong p16 INK4a promoter activation in vivo display features of senescence
Liu, J.-Y., Souroullas, G. P., Diekman, B. O., Krishnamurthy, J., Hall, B. M., Sorrentino, J. A., Parker, J. S., Sessions, G. A., Gudkov, A. V., & Sharpless, N. E. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818313116 · Cited by 306
Pluquet, O., Pourtier, A., & Abbadie, C. (2015) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00334.2014 · Cited by 305
Regulation of Dendritic Cell Migration by CD74, the MHC Class II-Associated Invariant Chain
Faure-André, G., Vargas, P., Yuseff, M.-I., Heuzé, M. L., Diaz, J., Lankar, D., Steri, V., Manry, J., Hugues, S., Vascotto, F., et al. (2008) · Science · doi:10.1126/science.1159894 · Cited by 299
Cellular Senescence in the Kidney
Docherty, M.-H., O’Sullivan, E. D., Bonventre, J. V., & Ferenbach, D. A. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2018121251 · Cited by 291
Advanced CUBIC tissue clearing for whole-organ cell profiling
Matsumoto, K., Mitani, T. T., Horiguchi, S. A., Kaneshiro, J., Murakami, T. C., Mano, T., Fujishima, H., Konno, A., Watanabe, T. M., Hirai, H., et al. (2019) · Nature Protocols · doi:10.1038/s41596-019-0240-9 · Cited by 282
Self-citationNeutrophils contribute to spontaneous resolution of liver inflammation and fibrosis via microRNA-223
Calvente, C. J., Tameda, M., Johnson, C. D., del Pilar, H., Lin, Y. C., Adronikou, N., De Mollerat Du Jeu, X., Llorente, C., Boyer, J., & Feldstein, A. E. (2019) · Journal of Clinical Investigation · doi:10.1172/jci122258 · Cited by 268
Macrophages in age-related chronic inflammatory diseases
Oishi, Y., & Manabe, I. (2016) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2016.18 · Cited by 262
Clonal Analysis of Mouse Development Reveals a Polyclonal Origin for Yolk Sac Blood Islands
Ueno, H., & Weissman, I. L. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.08.001 · Cited by 247
Self-citationWhole-Body Profiling of Cancer Metastasis with Single-Cell Resolution
Kubota, S. I., Takahashi, K., Nishida, J., Morishita, Y., Ehata, S., Tainaka, K., Miyazono, K., & Ueda, H. R. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.06.010 · Cited by 245
Self-citationSingle-cell RNA-sequencing: The future of genome biology is now
Picelli, S. (2016) · RNA Biology · doi:10.1080/15476286.2016.1201618 · Cited by 237
AP-1 imprints a reversible transcriptional programme of senescent cells.
Martínez-Zamudio, R. I., Roux, P.-F., de Freitas, J. A. N. L. F., Robinson, L., Doré, G., Sun, B., Belenki, D., Milanovic, M., Herbig, U., Schmitt, C. A., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0529-5 · Cited by 236
Papatheodoridi, A., Chrysavgis, L., Koutsilieris, M., & Chatzigeorgiou, A. (2019) · Hepatology · doi:10.1002/hep.30834 · Cited by 210
Macrophage p38α promotes nutritional steatohepatitis through M1 polarization
Zhang, X., Fan, L., Wu, J., Xu, H., Leung, W. Y., Fu, K., Wu, J., Liu, K., Man, K., Yang, X., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.03.014 · Cited by 205
Vascular smooth muscle cell senescence in atherosclerosis
GORENNE, I., KAVURMA, M., SCOTT, S., & BENNETT, M. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.06.004 · Cited by 196
Carroll, B., Nelson, G., Rabanal‐Ruiz, Y., Kucheryavenko, O., Dunhill-Turner, N. A., Chesterman, C. C., Zahari, Q., Zhang, T., Conduit, S. E., Mitchell, C. A., et al. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201610113 · Cited by 188
Necessary and Sufficient Role for a Mitosis Skip in Senescence Induction
Johmura, Y., Shimada, M., Misaki, T., Naiki-Ito, A., Miyoshi, H., Motoyama, N., Ohtani, N., Hara, E., Nakamura, M., Morita, A., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.003 · Cited by 182
Self-citationSenescence in chronic liver disease: Is the future in aging?
Aravinthan, A. D., & Alexander, G. J. M. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.05.030 · Cited by 174
Real-time in vivo imaging of p16Ink4a reveals cross talk with p53
Yamakoshi, K., Takahashi, A., Hirota, F., Nakayama, R., Ishimaru, N., Kubo, Y., Mann, D. J., Ohmura, M., Hirao, A., Saya, H., et al. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200904105 · Cited by 172
Le, O. N. L., Rodier, F., Fontaine, F., Coppe, J., Campisi, J., DeGregori, J., Laverdière, C., Kokta, V., Haddad, E., & Beauséjour, C. M. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00567.x · Cited by 168
Bäumer, S., Keller, L., Holtmann, A., Funke, R., August, B. K., Gamp, A. C., Wolburg, H., Wolburg‐Buchholz, K., Deutsch, U., & Vestweber, D. (2006) · Blood · doi:10.1182/blood-2006-01-0141 · Cited by 162
Mitochondria: Are they causal players in cellular senescence?
Correia-Melo, C., & Passos, J. F. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.017 · Cited by 160
Senescent cell turnover slows with age providing an explanation for the Gompertz law
Karin, O., Agrawal, A., Porat, Z., Krizhanovsky, V., & Alon, U. (2019) · Nature Communications · doi:10.1038/s41467-019-13192-4 · Cited by 151
Profiling of m6A RNA modifications identified an age‐associated regulation of AGO 2 mRNA stability
Min, K., Zealy, R. W., Davila, S., Fomin, M., Cummings, J. C., Makowsky, D., Mcdowell, C. H., Thigpen, H., Hafner, M., Kwon, S., et al. (2018) · Aging Cell · doi:10.1111/acel.12753 · Cited by 131
Megquier, K., Turner-Maier, J., Swofford, R., Kim, J. H., Sarver, A. L., Wang, C., Sakthikumar, S., Johnson, J., Koltookian, M., Lewellen, M., et al. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0221 · Cited by 120
The regulation of proximal tubular salt transport in hypertension: an update
Wang, X., Armando, I., Upadhyay, K. K., Pascua, A., & José, P. A. (2009) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e32832f5775 · Cited by 90
Senescent cells are resistant to death despite low Bcl-2 level
Sasaki, M., Kumazaki, T., Takano, H., Nishiyama, M., & Mitsui, Y. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00281-0 · Cited by 88
Araki, H., Knapp, C., Tsai, P., & Print, C. G. (2012) · FEBS Open Bio · doi:10.1016/j.fob.2012.04.003 · Cited by 79
Real-time in vivo imaging of P16[INK]⁴[a] reveals cross talk with p53
Hara, E. (2010) · Medical Entomology and Zoology · Cited by 72
p16(INK4a) and p53 deficiency cooperate in tumorigenesis.
Sharpless, N. E., Alson, S., Chan, S., Silver, D. P., Castrillón, D. H., & DePinho, R. A. (2002) · PubMed · Cited by 63
Paolillo, C., Londin, E. R., & Fortina, P. M. (2019) · Clinical Chemistry · doi:10.1373/clinchem.2017.283895 · Cited by 63
A Single Cell Transcriptomic Atlas Characterizes Aging Tissues in the MousePreprint
Pisco, A. O., McGeever, A., Schaum, N., Karkanias, J., Neff, N. F., Darmanis, S., Wyss‐Coray, T., & Quake, S. R. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/661728 · Cited by 57
Sessions, G. A., Copp, M. E., Liu, J., Sinkler, M. A., D’Costa, S., & Diekman, B. O. (2019) · The FASEB Journal · doi:10.1096/fj.201900815rr · Cited by 52
Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response
Iwasaki, K., Komiya, H., Kakizaki, M., Miyoshi, C., Abe, M., Sakimura, K., Funato, H., & Yanagisawa, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00535 · Cited by 47
Self-citationKamimoto, K., Nakano, Y., Kaneko, K., Miyajima, A., & Itoh, T. (2020) · Communications Biology · doi:10.1038/s42003-020-1006-1 · Cited by 46
Self-citationDulic, V. (2013) · Methods in Molecular Biology · doi:10.1007/978-1-62703-239-1_2 · Cited by 42
A cancer rainbow mouse for visualizing the functional genomics of oncogenic clonal expansion
Boone, P. G., Rochelle, L. K., Ginzel, J. D., Lubkov, V., Roberts, W. L., NICHOLLS, P. J., Bock, C. B., Flowers, M. L., von Furstenberg, R. J., Stripp, B. R., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13330-y · Cited by 42
Scarff, K. L., Ung, K. S., Sun, J., & Bird, P. I. (2003) · genesis · doi:10.1002/gene.10210 · Cited by 33
Aging promotes neoplastic disease through effects on the tissue microenvironment
Marongiu, F., Serra, M. P., Doratiotto, S., Sini, M., Fanti, M., Cadoni, E., Serra, M., & Laconi, E. (2016) · Aging · doi:10.18632/aging.101128 · Cited by 30
Schmidt‐Supprian, M., Wunderlich, F. T., & Rajewsky, K. (2007) · Transgenic Research · doi:10.1007/s11248-007-9100-4 · Cited by 24
Jumonji C Demethylases in Cellular Senescence
Leon, K. E., & Aird, K. M. (2019) · Genes · doi:10.3390/genes10010033 · Cited by 22
El‐Nachef, D., Shi, K. Y., Beussman, K. M., Martinez, R. A., Regier, M. C., Everett, G. W., Murry, C. E., Stevens, K. R., Young, J. E., Sniadecki, N. J., et al. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.06.005 · Cited by 22
Kan, C.-Y., Wen, V. W., Pasquier, E., Jankowski, K., Chang, M. H. Y., Richards, L. A., Kavallaris, M., & MacKenzie, K. L. (2012) · Oncogene · doi:10.1038/onc.2011.645 · Cited by 16
Mitochondrial Damage Induces Senescence with a Twisted Arm
Fernández-Marcos, P. J., & Serrano, M. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.01.012 · Cited by 8
Sentinel p16 INK4a + cells in the basement membrane form a reparative niche in the lungPreprint
de Mochel, N. R., Cheong, K. N., Cassandras, M., Wang, C., Krasilnikov, M., Matatia, P. R., Molofsky, A. B., Campisi, J., & Peng, T. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.10.142893 · Cited by 6
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
