肺泡上皮再生对于正常肺功能至关重要，但在疾病中会出现失调。虽然 2 型肺泡 (AT2) 和棒状细胞是已知的远端肺上皮祖细胞，但由于缺乏标记 AT1 细胞的高度特异性小鼠模型，确定 1 型肺泡上皮 (AT1) 细胞是否也有助于肺泡再生受到阻碍。为了解决这个问题，生成了 Gramd2 CreERT2 转基因品系并将其与 Rosa mTmG 小鼠杂交。广泛的细胞表征，包括远端肺免疫荧光和细胞离心涂片染色，证实 GRAMD2 AT1 细胞高度富集绿色荧光蛋白 (GFP)。有趣的是，Gramd2 CreERT2 GFP 细胞能够在与 Mlg 成纤维细胞共培养的类器官中形成类器官。时间 scRNAseq 显示，Gramd2 AT1 细胞在获得增殖能力的同时，会在多种中间肺上皮细胞状态（包括类器官中的基底细胞、分泌细胞和 AT2 细胞）之间转变。我们的结果表明 Gramd2 AT1 细胞具有高度可塑性，表明它们可能有助于肺泡再生。

Alveolar epithelial regeneration is critical for normal lung function and becomes dysregulated in disease. While alveolar type 2 (AT2) and club cells are known distal lung epithelial progenitors, determining if alveolar epithelial type 1 (AT1) cells also contribute to alveolar regeneration has been hampered by lack of highly specific mouse models labeling AT1 cells. To address this, the Gramd2 CreERT2 transgenic strain was generated and crossed to Rosa mTmG mice. Extensive cellular characterization, including distal lung immunofluorescence and cytospin staining, confirmed that GRAMD2 + AT1 cells are highly enriched for green fluorescent protein (GFP). Interestingly, Gramd2 CreERT2 GFP + cells were able to form organoids in organoid co-culture with Mlg fibroblasts. Temporal scRNAseq revealed that Gramd2 + AT1 cells transition through numerous intermediate lung epithelial cell states including basal, secretory and AT2 cell in organoids while acquiring proliferative capacity. Our results indicate that Gramd2 + AT1 cells are highly plastic suggesting they may contribute to alveolar regeneration.