Yu Xuexin, Feng Lin, Han Zujing, Wu Bo, Wang Shuyuan, Xiao Yun, Li Feng, Zhang Lianfeng, Cao Bangrong, Di Xuebing, Lu Dan, Li Xia, Jiang Wei, Zhang Kaitai, Cheng Shujun
College of Bioinformatics Science and Technology, Harbin Medical University, 194 Xuefu Road, Harbin, 150081, China.
Mol Biosyst. 2016 Apr;12(4):1342-9. doi: 10.1039/c5mb00881f. Epub 2016 Feb 29.
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 HiSeq™ 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.
肺发育遵循一系列复杂的动态组织发生事件，这些事件依赖于基因表达的波动，而基因调控的破坏可能导致毁灭性后果，如成年期疾病。为了研究肺发育的机制，我们使用Illumina HiSeq™ 2000进行RNA测序，以测量9只恒河猴肺组织中的mRNA表达，这些恒河猴涵盖了从妊娠45天的胎儿到出生后7天的个体。这个发育时期分为三个发育阶段，包括早期（妊娠45 - 100天）、中期（妊娠137 - 163天）和晚期（出生后4 - 7天）。首先，我们鉴定了阶段特异性基因，基于此发现早期的主要生物学过程主要与内部生长信号相关，而中期和晚期特异性基因控制外部应激信号。然后，我们构建了阶段特异性蛋白质 - 蛋白质相互作用（PPI）子网，提取了动态模块，并鉴定了模块之间的串扰。此外，我们发现了四条可以介导串扰的活跃途径，包括Notch信号通路、细胞周期、NOD样受体信号通路和Toll样受体信号通路。这些途径不仅在肺发育中起关键作用，还与肺部疾病有关。最后，发现了一些重要的桥梁分子，如PSEN2、HSP90AA1和CASP8，以解释串扰的潜在机制。因此，我们的研究展示了恒河猴肺发育的基因表达图谱，并为肺发育机制提供了更深入的见解。
