Tissue repair requires a highly coordinated cellular response to injury. In the lung, alveolar type 2 cells (AT2s) act as stem cells to replenish both themselves and alveolar type 1 cells (AT1s); however, the complex orchestration of stem cell activity after injury is poorly understood. Here, we establish longitudinal imaging of AT2s in murine intact tissues ex vivo and in vivo in order to track their dynamic behavior over time. We discover that a large fraction of AT2s become motile following injury and provide direct evidence for their migration between alveolar units. High-resolution morphokinetic mapping of AT2s further uncovers the emergence of distinct motile phenotypes. Inhibition of AT2 migration via genetic depletion of ArpC3 leads to impaired regeneration of AT2s and AT1s in vivo. Together, our results establish a requirement for stem cell migration between alveolar units and identify properties of stem cell motility at high cellular resolution.

组织修复需要高度协调的细胞对损伤的反应。在肺中，肺泡 2 型细胞 (AT2) 充当干细胞来补充自身和肺泡 1 型细胞 (AT1)；然而，人们对损伤后干细胞活性的复杂协调知之甚少。在这里，我们在小鼠完整组织中离体和体内建立了 AT2 的纵向成像，以跟踪它们随时间的动态行为。我们发现大部分 AT2 在受伤后变得能动，并为它们在肺泡单位之间迁移提供了直接证据。 AT2 的高分辨率形态动力学图谱进一步揭示了不同运动表型的出现。通过ArpC3基因缺失来抑制 AT2 迁移会导致 AT2 和 AT1体内再生受损。总之，我们的结果确立了干细胞在肺泡单位之间迁移的要求，并以高细胞分辨率识别干细胞运动的特性。