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<p>Bronchioalveolar stem cells (BASCs), located at the bronchioalveolar duct junction (BADJ), contribute to adult lung regeneration after injury, yet their role during postnatal lung morphogenesis remains poorly characterized. In this study, we showed that BASCs first emerged at birth and persisted throughout the postnatal saccular stage with stable localization and abundance. To trace their fate, we generated a <i>Sftpc</i><sup><i>DreER</i></sup> knock-in mouse and combined it with <i>Scgb1a1</i><sup><i>CreER</i></sup> and dual-reporter <i>H11</i><sup><i>LSL − ZsG_RSR−tdT</i></sup> mice to establish a dual recombinase-mediated lineage tracing system (BASC-Tracer). Using this system, we observed that BASCs expanded postnatally and migrated into both alveolar and airway compartments. In the alveoli, they lost SCGB1A1 expression and differentiated into AT2 and AT1 cells to drive alveolar maturation, whereas in the airways, they lost SFTPC expression and gave rise to club cells. Furthermore, we employed a hyperoxia-induced bronchopulmonary dysplasia model to assess the injury response of BASCs during lung development. We found that hyperoxic exposure markedly suppresses BASC regenerative capacity. Finally, spatial transcriptomic analysis revealed that BASCs reside within a distinct BADJ-associated niche, characterized by a unique repertoire of signaling ligands that distinguishes this niche from those of AT2 and club cells. Together, these findings delineate the dynamic behavior of BASCs during lung development and provide spatial characterization of their niche.</p>

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Developmental dynamics of bronchioalveolar stem cells revealed by dual-reporter lineage tracing

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月13日

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  • Yuanshu Li,
  • Jiaqi Liu,
  • Shuilian Chi,
  • Rongrong Lv,
  • Haowen Wang,
  • Li Jiang,
  • Yulong Xie,
  • Chaoqun Wang

摘要

Bronchioalveolar stem cells (BASCs), located at the bronchioalveolar duct junction (BADJ), contribute to adult lung regeneration after injury, yet their role during postnatal lung morphogenesis remains poorly characterized. In this study, we showed that BASCs first emerged at birth and persisted throughout the postnatal saccular stage with stable localization and abundance. To trace their fate, we generated a SftpcDreER knock-in mouse and combined it with Scgb1a1CreER and dual-reporter H11LSL − ZsG_RSR−tdT mice to establish a dual recombinase-mediated lineage tracing system (BASC-Tracer). Using this system, we observed that BASCs expanded postnatally and migrated into both alveolar and airway compartments. In the alveoli, they lost SCGB1A1 expression and differentiated into AT2 and AT1 cells to drive alveolar maturation, whereas in the airways, they lost SFTPC expression and gave rise to club cells. Furthermore, we employed a hyperoxia-induced bronchopulmonary dysplasia model to assess the injury response of BASCs during lung development. We found that hyperoxic exposure markedly suppresses BASC regenerative capacity. Finally, spatial transcriptomic analysis revealed that BASCs reside within a distinct BADJ-associated niche, characterized by a unique repertoire of signaling ligands that distinguishes this niche from those of AT2 and club cells. Together, these findings delineate the dynamic behavior of BASCs during lung development and provide spatial characterization of their niche.