Fetal Tracheal Occlusion Increases Lung Basal Cells via Increased Yap Signaling.
Fetal Tracheal Occlusion Increases Lung Basal Cells via Increased Yap Signaling.
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DOI：
10.3389/fped.2021.780166
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发表时间：
2021
影响因子：
2.6
通讯作者：
Varisco BM
中科院分区：
文献类型：
--
作者：
Serapiglia V;Stephens CA;Joshi R;Aydin E;Oria M;Marotta M;Peiro JL;Varisco BM
胎儿气管内窥镜闭塞（FETO）是一种新兴的手术治疗先天性膈疝（CDH）。绵羊和家兔的数据表明，气管闭塞（TO）后肺上皮细胞群发生改变，转录组特征涉及基底细胞。为了验证这一假设，我们对胎儿兔肺To进行了反卷积测序（mRNA-seq）数据并进行了定量图像分析，发现To后基底细胞增加，纤毛细胞减少。在胎儿小鼠TO模型中，流式细胞术显示基底细胞增加，免疫组织化学显示基底细胞延伸到胸膜下气道。核Yap，一种已知的基底细胞命运的调节剂，在TO肺中增加，肺上皮上的Yap消融消除了TO介导的基底细胞扩增。TO肺mRNA-seq显示下游Yap基因活性升高。先天性和胎儿气管闭塞的人肺标本胸膜下基底细胞群，在对照组中不存在。TO增加肺上皮细胞核Yap，导致基底细胞扩增。
Fetal endoscopic tracheal occlusion (FETO) is an emerging surgical therapy for congenital diaphragmatic hernia (CDH). Ovine and rabbit data suggested altered lung epithelial cell populations after tracheal occlusion (TO) with transcriptomic signatures implicating basal cells. To test this hypothesis, we deconvolved mRNA sequencing (mRNA-seq) data and used quantitative image analysis in fetal rabbit lung TO, which had increased basal cells and reduced ciliated cells after TO. In a fetal mouse TO model, flow cytometry showed increased basal cells, and immunohistochemistry demonstrated basal cell extension to subpleural airways. Nuclear Yap, a known regulator of basal cell fate, was increased in TO lung, and Yap ablation on the lung epithelium abrogated TO-mediated basal cell expansion. mRNA-seq of TO lung showed increased activity of downstream Yap genes. Human lung specimens with congenital and fetal tracheal occlusion had clusters of subpleural basal cells that were not present in the control. TO increases lung epithelial cell nuclear Yap, leading to basal cell expansion.
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影响因子：
10.5
作者：
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通讯作者：
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DOI：
10.1152/ajplung.00342.2004
发表时间：
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影响因子：
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作者：
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