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Crosstalk of dynamic functional modules in lung development of rhesus macaques

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机构: [a]College of Bioinformatics Science and Technology, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, China. E-mail: chengshj@263.net.cn [b]State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute & Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China [c]BGI Tech Solutions Co., Ltd, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China [d]Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China [e]Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China [f]Department of Basic Research, Sichuan Cancer Hospital and Institute, Chengdu, 610041, China
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Lung development follows a complex series of dynamic histogenic events that depend on the fluctuation of gene expression, and the disruption of gene regulation could lead to devastating consequences, such as diseases in adulthood. In order to investigate the mechanism of lung development, we performed RNA sequencing by Illumina HiSeqt 2000 to measure mRNA expression in lung tissues of nine rhesus macaques spanning from foetuses at gestation of 45 days to postnatal at 7 days. This development period was divided into three developmental stages, including the early stage (45-100 gestational days), the middle stage (137-163 gestational days) and the late stage (after birth at 4-7 days). Firstly, we identified stage-specific genes, based on which we found that the principle biological processes of the early stage were mainly associated with internal growth signalling, while the middle and late stage-specific genes controlled the external stress signalling. Then, we constructed a stage-specific protein-protein interaction (PPI) subnetwork, extracted dynamic modules, and identified crosstalk between modules. Moreover, we found four active pathways that could mediate the crosstalk, including the Notch signalling pathway, cell cycle, NOD-like receptor signalling pathway, and Toll-like receptor signalling pathway. These pathways not only played crucial roles in lung development, but also were implicated in lung diseases. Finally, some important bridgers, such as PSEN2, HSP90AA1 and CASP8, were discovered to explain the potential mechanism of crosstalk. Therefore, our study presents the landscape of gene expression of lung development of rhesus macaques, and provides an extended insight into the lung development mechanism.

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基金编号: 2014AA021102 2014AA020602

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出版当年[2016]版:
大类 | 3 区 生物
小类 | 3 区 生化与分子生物学
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Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
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第一作者机构: [a]College of Bioinformatics Science and Technology, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, China. E-mail: chengshj@263.net.cn
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通讯机构: [a]College of Bioinformatics Science and Technology, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, China. E-mail: chengshj@263.net.cn [b]State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute & Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China
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