PDF(Pubmed)
Abstract：
Studying human fetal lungs can inform how developmental defects and disease states alter the function of the lungs. Here, we sequenced >150,000 single cells from 19 healthy human pseudoglandular fetal lung tissues ranging between gestational weeks 10-19. We capture dynamic developmental trajectories from progenitor cells that express abundant levels of the cystic fibrosis conductance transmembrane regulator (CFTR). These cells give rise to multiple specialized epithelial cell types. Combined with spatial transcriptomics, we show temporal regulation of key signalling pathways that may drive the temporal and spatial emergence of specialized epithelial cells including ciliated and pulmonary neuroendocrine cells. Finally, we show that human pluripotent stem cell-derived fetal lung models contain CFTR-expressing progenitor cells that capture similar lineage developmental trajectories as identified in the native tissue. Overall, this study provides a comprehensive single-cell atlas of the developing human lung, outlining the temporal and spatial complexities of cell lineage development and benchmarks fetal lung cultures from human pluripotent stem cell differentiations to similar developmental window.
摘要：
研究人类胎儿肺可以告知发育缺陷和疾病状态如何改变肺的功能。这里,我们对来自19个健康人类假腺体胎儿肺组织的>150,000个单细胞进行了测序，范围在10-19周之间。我们从表达丰富水平的囊性纤维化电导跨膜调节因子（CFTR）的祖细胞中捕获动态发育轨迹。这些细胞产生多种特化的上皮细胞类型。结合空间转录组学，我们显示了关键信号通路的时间调节，这些信号通路可能驱动包括纤毛和肺神经内分泌细胞在内的特化上皮细胞的时间和空间出现。最后,我们表明,人多能干细胞来源的胎儿肺模型含有表达CFTR的祖细胞,这些祖细胞捕获了与天然组织中鉴定的相似的谱系发育轨迹.总的来说,这项研究提供了发育中的人类肺的全面单细胞图谱，概述了细胞谱系发育的时间和空间复杂性，并从人类多能干细胞分化到相似的发育窗口对胎儿肺培养物进行了基准。
