Lung injury in mice induces mobilization of discrete subsets of epithelial progenitor cells to promote new airway and alveolar structures. However, whether similar cell types exist in human lung remains unresolved. Using flow cytometry, we identified a distinct cluster of cells expressing epithelial cell adhesion molecule (EpCAM), a cell surface marker expressed on epithelial progenitor cells, enriched in the ecto-5'-nucleotidase CD73 in unaffected postnatal human lung resected from pediatric patients with congenital lung lesions. Within the EpCAM⁺CD73⁺ population, a small subset co-express integrin β4 and HTII-280. This population remained stable with age. Spatially, EpCAM⁺CD73⁺ cells were positioned along the basal membrane of respiratory epithelium and alveolus next to CD73⁺ cells lacking EpCAM. Expanded EpCAM⁺CD73⁺ cells give rise to pseudostratified epithelium in 2D air-liquid interface or a clonal 3D organoid assay. Organoids generated under alveolar differentiation conditions were cystic-like and lacked robust alveolar mature cell types. Compared with unaffected postnatal lung, congenital lung lesions were marked by clusters of EpCAM⁺CD73⁺ cells in airway and cystic distal lung structures lined by simple epithelium of composed of EpCAM⁺SCGB1A1⁺ cells and hyperplastic EpCAM⁺proSPC⁺ cells. In non-small cell lung cancer (NSCLC), there was a marked increase in EpCAM⁺CD73⁺ tumor cells enriched in inhibitory immune checkpoint molecules CD47 and programmed death-ligand 1 (PD-L1), which was associated with poor survival in lung adenocarcinoma. In conclusion, EpCAM⁺CD73⁺ cells are a rare novel epithelial progenitor cell in human lung. Importantly, re-emergence of CD73 in lung adenocarcinoma enriched in negative immune checkpoint molecules may serve as a novel therapeutic target.

中文翻译：

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EpCAM + CD73 +标记人后肺中的上皮祖细胞，并与包括肺腺癌在内的肺部疾病的发病机制有关。

小鼠的肺损伤诱导上皮祖细胞离散亚群的动员，以促进新的气道和肺泡结构。然而，人类肺中是否存在相似的细胞类型仍未得到解决。使用流式细胞仪，我们确定了表达上皮细胞粘附分子（EpCAM）的独特细胞簇，EpCAM是在上皮祖细胞上表达的细胞表面标志物，在未患儿的小儿肺癌患者中切除了富含ecto-5'-核苷酸酶CD73。先天性肺部病变。在EpCAM ⁺ CD73 ⁺群体中，一小部分共表达整联蛋白β4和HTII-280。该人口随着年龄的增长保持稳定。在空间上，EpCAM ⁺ CD73 ⁺细胞沿呼吸道上皮和肺泡的基底膜定位，紧靠缺少EpCAM的CD73 ⁺细胞。扩展的EpCAM ⁺ CD73 ⁺细胞在2D气液界面或3D克隆类器官测定法中产生假复层上皮。在肺泡分化条件下产生的类器官是囊性的，并且缺乏健壮的肺泡成熟细胞类型。与未受影响的产后肺相比，先天性肺病变的特征是气道中的EpCAM ⁺ CD73 ⁺细胞簇和由简单的上皮组成的囊性远端肺结构，由EpCAM ⁺ SCGB1A1 ⁺细胞和增生性EpCAM ⁺ proSPC ^+组成细胞。在非小细胞肺癌（NSCLC）中，富含抑制性免疫检查点分子CD47和程序性死亡配体1（PD-L1）的EpCAM ⁺ CD73 ⁺肿瘤细胞显着增加，这与肺存活不良有关腺癌。总之，EpCAM ⁺ CD73 ⁺细胞是人肺中一种罕见的新型上皮祖细胞。重要的是，CD73在富含阴性免疫检查点分子的肺腺癌中的重新出现可能充当了新的治疗目标。