YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1.
YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1.
复制标题
雅普通过NFIB/KLF 5/NKX 2 -1调节肺泡上皮细胞分化和AGER。
DOI：
10.1016/j.isci.2021.102967
复制
发表时间：
2021-09-24
期刊：
影响因子：
5.8
通讯作者：
Whitsett JA
中科院分区：
文献类型：
--
作者：
Gokey JJ;Snowball J;Sridharan A;Sudha P;Kitzmiller JA;Xu Y;Whitsett JA
通气依赖于由两种主要上皮细胞类型（肺泡1型（AT 1）和2型（AT 2）细胞）内衬的肺泡。AT 1细胞介导气体交换，而AT 2细胞合成和分泌肺表面活性剂，并作为修复肺泡的祖细胞。我们开发了转基因小鼠，其中雅普被激活或删除，以确定其在肺泡上皮细胞分化中的作用。出生后雅普激活增加了上皮细胞增殖，增加了AT 1细胞数量，并导致表达非典型基因的肺泡细胞亚群分化不确定，这些基因通常仅限于气道上皮细胞。雅普缺失增加了与成熟AT 2细胞相关的基因的表达。雅普激活增强了转录因子启动子中的DNA可及性，基序富集分析预测了与肺泡细胞分化相关的靶基因。雅普与KLF 5、NFIB和NKX 2 -1共同参与AGER的调控。雅普在调节肺泡上皮分化的转录网络中起着核心作用。雅普、TEAD、NKX 2 -1、KLF 5和NFIB相互作用以增加AGER的表达活性雅普表达诱导染色质区域的可接近性的广泛增加雅普缺失增强成熟AT 2细胞标志物的表达雅普激活增加AT 1细胞相关基因的表达和AT 1细胞的数量遗传学;发育遗传学;分子生物学
Ventilation is dependent upon pulmonary alveoli lined by two major epithelial cell types, alveolar type-1 (AT1) and 2 (AT2) cells. AT1 cells mediate gas exchange while AT2 cells synthesize and secrete pulmonary surfactants and serve as progenitor cells which repair the alveoli. We developed transgenic mice in which YAP was activated or deleted to determine its roles in alveolar epithelial cell differentiation. Postnatal YAP activation increased epithelial cell proliferation, increased AT1 cell numbers, and caused indeterminate differentiation of subsets of alveolar cells expressing atypical genes normally restricted to airway epithelial cells. YAP deletion increased expression of genes associated with mature AT2 cells. YAP activation enhanced DNA accessibility in promoters of transcription factors and motif enrichment analysis predicted target genes associated with alveolar cell differentiation. YAP participated with KLF5, NFIB, and NKX2-1 to regulate AGER. YAP plays a central role in a transcriptional network that regulates alveolar epithelial differentiation. YAP, TEAD, NKX2-1, KLF5 and NFIB interact to increase expression of AGER Active YAP expression induces widespread increased accessibility of chromatin regions YAP deletion enhances expression of mature AT2 cell markers YAP activation increases expression of AT1 cell related genes and number of AT1 cells Genetics; Developmental genetics; Molecular biology
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
2.7
作者：
Hsu YC;Osinski J;Campbell CE;Litwack ED;Wang D;Liu S;Bachurski CJ;Gronostajski RM
通讯作者：
Gronostajski RM
影响因子：
5.8
作者：
Barnett, Derek W.;Garrison, Erik K.;Marth, Gabor T.
通讯作者：
Marth, Gabor T.
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG
DOI：
10.1073/pnas.1813952116
发表时间：
2019-03-05
影响因子：
11.1
作者：
Frank, David B.;Penkala, Ian J.;Morrisey, Edward E.
通讯作者：
Morrisey, Edward E.