{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:15:56Z","timestamp":1788322556822,"version":"build-2803163510"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"19","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["19K08454"],"award-info":[{"award-number":["19K08454"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["DK11005"],"award-info":[{"award-number":["DK11005"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,5,13]]},"abstract":"<jats:p>\n                    Circadian regulation of the cell cycle progression generates a diurnal supply of newborn cells to replace those lost in organs and tissues. In this study, we analyzed circadian time-dependent changes in cell types within the mouse tongue epithelium. Using single-cell RNA sequencing, we observed circadian time-dependent changes in the populations of stem\/progenitor cells and the differentiated cells in mice tongues. Notably, we observed time-dependent changes in the type II taste cell population, which were abolished by ablation of taste bud stem cells, thereby inhibiting cell proliferation within the taste cell population. Through experiments with taste bud organoids (TBOs), we found a 24-h cell cycle period, which was disrupted by the knockdown of the core-clock gene\n                    <jats:italic toggle=\"yes\">Bmal1<\/jats:italic>\n                    . In TBOs, both cell divisions and apoptotic cells exhibited circadian time-dependent phenotypes. Interestingly, the time-dependent changes in cell death disappeared in the stem cell\u2013ablated TBOs, indicating that the diurnal supply of newly born cells is essential for the rhythmic cell death phenotype. Additionally, taste tests conducted at different times of the day revealed time-dependent sensitivity changes originating from type II taste cells in mice. These findings suggest that the time-dependent changes in taste cell population are driven by circadian clock\u2013regulated cell cycle progression and control time-dependent physiological regulation in the mouse tongue.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2421421122","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T14:14:27Z","timestamp":1746713667000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["Circadian clock\u2013gated cell renewal controls time-dependent changes in taste sensitivity"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9876-3086","authenticated-orcid":false,"given":"Toru","family":"Matsu-ura","sequence":"first","affiliation":[{"name":"Department of Pathology, Kansai Medical University","place":["Hirakata, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsunori","family":"Nasu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kansai Medical University","place":["Hirakata, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suengwon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neurobiology, University of Cincinnati","place":["Cincinnati"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9957-6901","authenticated-orcid":false,"given":"Naoko","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kansai Medical University","place":["Hirakata, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kansai Medical University","place":["Hirakata, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kansai Medical University","place":["Hirakata, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kae","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kansai Medical University","place":["Hirakata, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian I.","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neurobiology, University of Cincinnati","place":["Cincinnati"]},{"name":"Center for Stem Cell and Organoid Medicine, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center","place":["Cincinnati"]},{"name":"Center for Chronobiology, Cincinnati Children\u2019s Hospital Medical Center","place":["Cincinnati"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Tsuta","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kansai Medical University","place":["Hirakata, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319399111"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1181759"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65306-0"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209592109"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1215935110"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.06.022"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.9305"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1081\/CBI-120002594"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06685"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086271"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705576200"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213317110"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.10.015"},{"key":"e_1_3_4_14_2","first-page":"12","article-title":"Radiation response of the mouse tongue epithelium","volume":"7","author":"Moses R.","year":"1986","unstructured":"R. Moses, J. Kummermehr, Radiation response of the mouse tongue epithelium. Br. J. Cancer Suppl. 7, 12\u201315 (1986).","journal-title":"Br. J. Cancer Suppl."},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02899559"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep17185"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.4161\/fly.4.4.13010"},{"key":"e_1_3_4_18_2","first-page":"R931","article-title":"Circadian rhythm in recognition threshold of salt taste in healthy subjects","volume":"259","author":"Fujimura A.","year":"1990","unstructured":"A. Fujimura, H. Kajiyama, T. Tateishi, A. Ebihara, Circadian rhythm in recognition threshold of salt taste in healthy subjects. Am. J. Physiol. 259, R931\u2013R935 (1990).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1103"},{"key":"e_1_3_4_20_2","unstructured":"T. Matsu-ura Single-cell RNA-seq data from mouse tongue taste epithelium. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE293526. Accessed 23 April 2025."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.05.007"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.10.004"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.5.7896010"},{"key":"e_1_3_4_26_2","first-page":"195","article-title":"Circadian rhythms of DNA content in brain and kidney: Effects of environmental stimulation","volume":"15","author":"Grassi Zucconi G.","year":"1988","unstructured":"G. Grassi Zucconi, F. Carandente, E. Menichini, S. Belia, A. Giuditta, Circadian rhythms of DNA content in brain and kidney: Effects of environmental stimulation. Chronobiologia 15, 195\u2013204 (1988).","journal-title":"Chronobiologia"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204470119"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913256107"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703170114"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000792"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0340"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-020-00429-9"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-015-9821-x"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.045"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20207"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2421421122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T14:15:17Z","timestamp":1746713717000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2421421122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,8]]},"references-count":35,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2025,5,13]]}},"alternative-id":["10.1073\/pnas.2421421122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2421421122","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.03.09.531858","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,8]]},"assertion":[{"value":"2024-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2421421122"}}