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Robust longitudinal tracing using evProTracer in murine tracheal epithelium revealed near-complete homeostatic turnover (91.6\u2009\u00b1\u20091.29% epithelial replacement over 25 weeks), while basal cell-specific \u200bTrp63-evProTracer\u200b uncovered a dorsally biased proliferation pattern\u200b, contributing 33.88\u2009\u00b1\u20091.44% of total epithelial renewal over 6 months, with early differentiation bias toward club cells. These data demonstrate that ventral epithelial renewal is primarily mediated by non-basal facultative progenitors, revealing their constitutive activation during homeostasis. This study uncovers spatially stratified renewal hierarchies: dorsal basal stem cell reservoirs versus ventral facultative non-basal progenitors. evProTracer provides a versatile platform for investigating tissue plasticity hierarchies in regenerative organs.<\/jats:p>","DOI":"10.1186\/s13287-025-04888-0","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T08:06:34Z","timestamp":1767773194000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced proliferation tracer reveals Dorsal-Ventral asymmetry in tracheal epithelial Renewal\u200b"],"prefix":"10.1186","volume":"17","author":[{"given":"Haiyuan","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazhu","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"4888_CR1","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1152\/physrev.1956.36.2.255","volume":"36","author":"E Bruce","year":"1956","unstructured":"Bruce E, Walker CPL. 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The approved project, entitled \u200b\u200b\"Targeting Pulmonary Cells Using Dual Homologous Recombination System in Mice\"\u200b, was carried out under the supervision of \u200bPrinciple Investigator Yu Wei\u200b at the \u200bLaboratory Animal Center of Yunnan University. The entire experimental process adhered to established animal welfare standards, ensuring humane treatment and minimizing distress. This study aligns with the ethical principles of replacement, reduction, and refinement (3Rs) in animal research.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"69"}}