PDF(Pubmed)
Abstract：
Alveologenesis, the final stage in lung development, substantially remodels the distal lung, expanding the alveolar surface area for efficient gas exchange. Secondary crest myofibroblasts (SCMF) exist transiently in the neonatal distal lung and are crucial for alveologenesis. However, the pathways that regulate SCMF function, proliferation and temporal identity remain poorly understood. To address this, we purified SCMFs from reporter mice, performed bulk RNA-seq and found dynamic changes in Hippo-signaling components during alveologenesis. We deleted the Hippo effectors Yap/Taz from Acta2-expressing cells at the onset of alveologenesis, causing a significant arrest in alveolar development. Using single cell RNA-seq, we identified a distinct cluster of cells in mutant lungs with altered expression of marker genes associated with proximal mesenchymal cell types, airway smooth muscle and alveolar duct myofibroblasts. In vitro studies confirmed that Yap/Taz regulates myofibroblast-associated gene signature and contractility. Together, our findings show that Yap/Taz is essential for maintaining functional myofibroblast identity during postnatal alveologenesis.
摘要：
Alveologenesis,肺发育的最后阶段，实质上重塑远端肺，扩大有效的气体交换肺泡表面积。继发性c肌成纤维细胞（SCMF）在新生儿远端肺中短暂存在，对肺泡形成至关重要。然而,调节SCMF功能的途径，扩散,和时间身份仍然知之甚少。为了解决这个问题，我们从报告小鼠中纯化了SCMF，进行批量RNA测序，并发现肺泡形成过程中Hippo信号成分的动态变化。我们删除了河马效应器，Yap/Taz,从肺泡形成开始时的Acta2表达细胞，导致肺泡发育严重停滞。使用scRNA-seq，我们在突变肺中发现了一个独特的细胞簇，与近端间充质细胞类型相关的标记基因表达改变，气道平滑肌（ASM），和肺泡管成肌纤维细胞（DMF）。体外研究证实Yap/Taz严格调节肌成纤维细胞相关基因签名和收缩性。一起,我们的研究结果表明,Yap/Taz对于在出生后肺泡形成过程中维持功能性肌成纤维细胞身份至关重要.
