Transitional cell states are at the crossroads of crucial developmental and regenerative events, yet little is known about how these states emerge and influence outcomes. The alveolar and airway epithelia arise from distal lung multipotent progenitors, which undergo cell fate transitions to form these distinct compartments. The identification and impact of cell states in the developing lung are poorly understood. Here, we identified a population of Icam1/Nkx2-1 epithelial progenitors harboring a transitional state program remarkably conserved in humans and mice during lung morphogenesis and regeneration. Lineage-tracing and functional analyses reveal their role as progenitors to both airways and alveolar cells and the requirement of this transitional program to make distal lung progenitors competent to undergo airway cell fate specification. The identification of a common progenitor cell state in vastly distinct processes suggests a unified program reiteratively regulating outcomes in development and regeneration.

中文翻译：

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形态发生和再生共享一个保守的核心过渡细胞状态程序，该程序控制肺上皮细胞的命运


过渡细胞状态处于关键发育和再生事件的十字路口，但人们对这些状态如何出现并影响结果知之甚少。肺泡和气道上皮起源于远端肺多能祖细胞，它们经历细胞命运转变以形成这些不同的隔室。对发育中的肺中细胞状态的识别和影响知之甚少。在这里，我们鉴定了一个 Icam1/Nkx2-1 上皮祖细胞种群，这些祖细胞在肺形态发生和再生过程中在人类和小鼠中携带着非常保守的过渡状态程序。谱系追踪和功能分析揭示了它们作为气道和肺泡细胞祖细胞的作用，以及这种过渡计划的要求，以使远端肺祖细胞能够进行气道细胞命运规范。在截然不同的过程中鉴定出共同的祖细胞状态，表明存在一个统一的程序，反复调节发育和再生的结果。