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<p>To elucidate spatiotemporal dynamics of tissue renewal, we developed evProTracer, an enhanced dual-recombinase lineage tracing system for cumulative in vivo labeling of proliferating cells. Robust longitudinal tracing using evProTracer in murine tracheal epithelium revealed near-complete homeostatic turnover (91.6 ± 1.29% epithelial replacement over 25 weeks), while basal cell-specific ​Trp63-evProTracer​ uncovered a dorsally biased proliferation pattern​, contributing 33.88 ± 1.44% 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.</p>

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Enhanced proliferation tracer reveals Dorsal-Ventral asymmetry in tracheal epithelial Renewal​

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月7日

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  • Haiyuan Chen,
  • Yazhu Zhong,
  • Hao Zhang,
  • Wei Yu

摘要

To elucidate spatiotemporal dynamics of tissue renewal, we developed evProTracer, an enhanced dual-recombinase lineage tracing system for cumulative in vivo labeling of proliferating cells. Robust longitudinal tracing using evProTracer in murine tracheal epithelium revealed near-complete homeostatic turnover (91.6 ± 1.29% epithelial replacement over 25 weeks), while basal cell-specific ​Trp63-evProTracer​ uncovered a dorsally biased proliferation pattern​, contributing 33.88 ± 1.44% 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.