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However, detecting mosaic STR mutations at single-cell resolution remains challenging due to both technical and biological complexities. To address this, we developed BayesMonSTR, a robust algorithm that enables accurate detection of mosaic STR mutations. Using this tool in single-cell analysis of human tissues, we reveal an accumulation of longer mosaic STR insertions and deletions (indels) in aging mitotic and post-mitotic cells. Strikingly, prefrontal cortex (PFC) neurons accumulate a higher burden of STR mutations than B cells or lung epithelium, with aged neurons exhibiting a particularly pronounced increase in longer STR deletions. These mutations are enriched at transcription start sites (TSSs) and active enhancers of highly expressed genes. Our work establishes a foundation for genome-wide, hypothesis-free discovery of disease-associated mosaic STR mutations and reveals a previously unexplored landscape of mosaic STR variation in development and aging.<\/jats:p>","DOI":"10.64898\/2026.02.04.703915","type":"posted-content","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T04:40:53Z","timestamp":1770439253000},"source":"Crossref","is-referenced-by-count":1,"title":["Unravelling genome-wide mosaic microsatellite mutations at single-cell resolution"],"prefix":"10.64898","author":[{"given":"Chunyi","family":"Wang","sequence":"first","affiliation":[{"name":"School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, 310024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxuan","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, 310024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixiang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, 310024, China"},{"name":"Fudan University, Shanghai, 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghe","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, 310024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhong","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Westlake University, 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