Human respiratory airway progenitors derived from pluripotent cells generate alveolar epithelial cells and model pulmonary fibrosis

Dataset of all figures in manuscript describing the following (abstract) Human lungs contain unique cell populations in distal respiratory airways and terminal bronchioles (RA/TRB) that accumulate in patients with lung injury and idiopathic pulmonary fibrosis (IPF), a lethal lung disease. As these populations are absent in rodents, deeper understanding requires a human in vitro model. Here we convert human pluripotent stem cells into expandable spheres, called induced respiratory airway progenitors (iRAPs), consisting of ~98% RA/TRB-associated cell types. One hPSC can give rise to 1010 iRAP cells. We differentiate iRAPs through a stage consistent with transitional type 2 alveolar epithelial (AT2) cells into a population corresponding to mature AT1 cells with 95% purity. iRAPs with deletion of HPS1, which causes pulmonary fibrosis in humans, replicate the aberrant differentiation and recruitment of profibrotic fibroblasts observed in IPF, indicating that intrinsic dysfunction of RA/TRB-associated alveolar progenitors contributes to HPS1-related IPF. iRAPs may provide a system suitable for IPF drug discovery and validation.本数据集涵盖某研究手稿中所有配图所对应的如下摘要内容：人类肺脏远端呼吸道与终末细支气管（RA/TRB）内存在独特细胞群，这类细胞群会在肺损伤患者及致死性肺部疾病特发性肺纤维化（idiopathic pulmonary fibrosis, IPF）患者体内异常蓄积。由于啮齿类动物体内不存在此类细胞群，因此对其开展深入研究需依托人类体外模型。本研究将人类多能干细胞（human pluripotent stem cells, hPSC）诱导为可扩增的细胞球，命名为诱导型呼吸道祖细胞（induced respiratory airway progenitors, iRAPs），该细胞群中约98%为RA/TRB相关细胞类型。单个人类多能干细胞可产生10^10个iRAP细胞。我们将iRAPs按照与过渡型2型肺泡上皮（AT2）细胞一致的分化阶段进行诱导，得到纯度达95%的成熟1型肺泡上皮（AT1）细胞对应群体。当iRAPs中存在导致人类肺纤维化的HPS1基因缺失时，其会重现IPF中观察到的异常分化以及促纤维化成纤维细胞的招募现象，这表明RA/TRB相关肺泡祖细胞的内在功能异常参与了HPS1相关IPF的发病过程。iRAPs可作为适用于IPF药物研发与验证的研究体系。