PMID- 37648885 OWN - NLM STAT- MEDLINE DCOM- 20230901 LR - 20231123 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 13 IP - 1 DP - 2023 Aug 30 TI - Single-cell RNA sequencing to detect age-associated genes that identify senescent cells in the liver of aged mice. PG - 14186 LID - 10.1038/s41598-023-41352-6 [doi] LID - 14186 AB - Senescent cells are predicted to occur and increase in animal tissues with aging. However, senescent cells in the tissues of aged animals remain to be identified. We refer to the marker genes to identify senescent cells in tissues as "age-associated genes". In this study, we searched for age-associated genes to identify senescent cells in the livers of aged animals. We performed single-cell RNA sequencing (scRNA-seq) to screen candidates for age-associated genes using young and aged rat primary hepatocytes. To remove animal species specificity, gene expression analyses in mouse livers were performed, confirming age-associated increases in the mRNA expression levels of Glipr1, Clec12a, and Phlda3. Moreover, the mRNA expression levels of Glipr1 and Phlda3 were increased by stress-induced premature senescence using doxorubicin in primary hepatocytes and livers of young mice. Transcriptome data of aged rat hepatocytes suggested that Glipr1, Clec12a, and Phlda3 were expressed in almost identical cells. Fluorescence in situ hybridization (FISH) confirmed the presence of cells with abundant Glipr1, Clec12a, and Phlda3 mRNA in 27-month-old mouse primary hepatocytes, which are considered to be senescent cells. This study is the first to identify Glipr1, Clec12a, and Phlda3 as age-associated genes in the mouse liver. CI - (c) 2023. Springer Nature Limited. FAU - Doshida, Yuta AU - Doshida Y AD - Molecular Regulation of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan. AD - Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, 192-0397, Japan. FAU - Hashimoto, Shinichi AU - Hashimoto S AD - Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, 641-8509, Japan. FAU - Iwabuchi, Sadahiro AU - Iwabuchi S AD - Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, 641-8509, Japan. FAU - Takino, Yuka AU - Takino Y AD - Molecular Regulation of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan. FAU - Ishiwata, Toshiyuki AU - Ishiwata T AD - Aging and Carcinogenesis, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, 173-0015, Japan. FAU - Aigaki, Toshiro AU - Aigaki T AD - Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, 192-0397, Japan. FAU - Ishigami, Akihito AU - Ishigami A AD - Molecular Regulation of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan. ishigami@tmig.or.jp. AD - Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, 192-0397, Japan. ishigami@tmig.or.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230830 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (RNA, Messenger) SB - IM MH - Mice MH - Rats MH - Animals MH - In Situ Hybridization, Fluorescence MH - *Liver MH - *Cellular Senescence/genetics MH - RNA, Messenger/genetics MH - Sequence Analysis, RNA PMC - PMC10468526 COIS- The authors declare no competing interests. EDAT- 2023/08/31 00:41 MHDA- 2023/09/01 06:43 PMCR- 2023/08/30 CRDT- 2023/08/30 23:32 PHST- 2022/12/23 00:00 [received] PHST- 2023/08/24 00:00 [accepted] PHST- 2023/09/01 06:43 [medline] PHST- 2023/08/31 00:41 [pubmed] PHST- 2023/08/30 23:32 [entrez] PHST- 2023/08/30 00:00 [pmc-release] AID - 10.1038/s41598-023-41352-6 [pii] AID - 41352 [pii] AID - 10.1038/s41598-023-41352-6 [doi] PST - epublish SO - Sci Rep. 2023 Aug 30;13(1):14186. doi: 10.1038/s41598-023-41352-6.