It has been challenging to generate in vitro models of alveolar lung diseases, as the stable culture of alveolar type 2 (AT2) cells has been difficult. Methods of generating and expanding AT2 cells derived from induced pluripotent stem cells (iPSCs) have been established and are expected to be applicable to disease modeling. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by dysfunction of lysosome-related organelles, such as lamellar bodies (LBs), in AT2 cells. From an HPS type 2 (HPS2) patient, we established disease-specific iPSCs (HPS2-iPSCs) and their gene-corrected counterparts. By live cell imaging, the LB dynamics were visualized and altered distribution, enlargement, and impaired secretion of LBs were demonstrated in HPS2-iPSC-derived AT2 cells. These findings provide insight into the AT2 dysfunction in HPS patients and support the potential use of human iPSC-derived AT2 cells for future research on alveolar lung diseases.

体外产生具有挑战性由于肺泡2型（AT2）细胞的稳定培养一直很困难，因此肺泡肺疾病的模型非常困难。已经建立了产生和扩增源自诱导多能干细胞（iPSC）的AT2细胞的方法，并有望将其应用于疾病建模。Hermansky-Pudlak综合征（HPS）是一种常染色体隐性遗传疾病，其特征在于AT2细胞中的溶酶体相关细胞器（如层状体（LBs））功能异常。我们从HPS 2型（HPS2）患者中，建立了疾病特异性iPSC（HPS2-iPSC）及其基因校正的对应物。通过活细胞成像，可以观察到LB动态，并在HPS2-iPSC衍生的AT2细胞中证实了LB的分布，扩大和分泌受损。