{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:42:16Z","timestamp":1785436936280,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U21A20198"],"award-info":[{"award-number":["U21A20198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["U21A20198"],"award-info":[{"award-number":["U21A20198"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cell lineage relationship studies in developmental and regenerative biology have been greatly advanced using techniques such as fluorescent labeling driven by cell-type-specific promoters. Nevertheless, unbiased non-invasive tools for distinguishing cell lineages are inevitably desired. Mitochondrial DNA (mtDNA) exhibits wide-range single-nucleotide polymorphisms (SNPs) among individual cells. Here, we aim to distinguish cell types in organs\/tissues of the same individual and in the regenerated liver based on the use of mtDNA SNPs. For this, two approaches\u2014\u201cMitochondrial Alteration Enrichment and Sequencing\u201d (MAESTER) and \u201cmitochondrial single-cell assay for transposase-accessible chromatin with sequencing\u201d (mtscATAC-seq)\u2014were adopted to facilitate the detection of mtDNA SNPs in single cells. With MAESTER, we show that specific cell types in the liver and spleen of the same individual can be successfully defined using collective individual-specific markers composed of panels of unique mtDNA SNP combinations. For its application, we performed partial hepatectomy (PH) on a Krt19:DreERT2\/+;R26:Rox-ZsGreen-Stop-Rox-tdTomato\/+ mouse harboring tdTomato-labeled cholangiocytes following tamoxifen injection and demonstrated that utilizing panels of unique mtDNA SNP combinations detected by mtscATAC-seq in the pre-PH cholangiocytes as markers can faithfully trace the cell fate in the post-PH liver samples. Hence, this approach may serve as an unbiased tool for investigating cell lineage relationships in relevant research areas such as liver regeneration.<\/jats:p>","DOI":"10.3390\/cells15100947","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T15:05:08Z","timestamp":1779721508000},"page":"947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Use of Single-Cell Mitochondrial DNA SNP Combinations for Distinguishing Organ-Specific Cell Types"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4085-1726","authenticated-orcid":false,"given":"Shuai","family":"Wang","sequence":"first","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Tu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0756-5613","authenticated-orcid":false,"given":"Haozhe","family":"Zhu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9804-261X","authenticated-orcid":false,"given":"Ce","family":"Gao","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Gao","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6160-7744","authenticated-orcid":false,"given":"Jinsong","family":"Wei","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6947-9668","authenticated-orcid":false,"given":"Hui","family":"Shi","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrong","family":"Peng","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Anderson, M.J., Naiche, L.A., Wilson, C.P., Elder, C., Swing, D.A., and Lewandoski, M. 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