A comprehensive transcriptomic view on the role of SMAD4 gene by RNAi-mediated knockdown in porcine follicular granulosa cells.
A comprehensive transcriptomic view on the role of SMAD4 gene by RNAi-mediated knockdown in porcine follicular granulosa cells.
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DOI：
10.1530/rep-16-0034
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发表时间：
2016-07
期刊：
影响因子：
3.8
通讯作者：
Lifan Zhang;Xing Du;Shengjuan Wei;Dongfeng Li;Qifa Li
中科院分区：
文献类型：
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作者：
Lifan Zhang;Xing Du;Shengjuan Wei;Dongfeng Li;Qifa Li
Sma和Mad-related protein 4（SMAD 4）作为转化生长因子β（TGF-β）信号通路的关键调节因子，与卵巢卵泡的发育密切相关，并在哺乳动物的生殖功能调控中发挥重要作用。然而，目前对SMAD 4基因在哺乳动物卵泡颗粒细胞（GC）中作用的全基因组观点的认识仍然很大程度上是未知的。在本研究中，进行RNA-Seq以研究通过RNA干扰（SMAD 4-siRNA）敲低SMAD 4在猪卵泡GC中的作用。与NC-siRNA处理组相比，SMAD 4-siRNA处理组GC中共检测到1025个差异表达基因（DEG），其中上调基因530个，下调基因495个。功能富集分析表明，SMAD 4-siRNA处理的细胞中表达上调的DEGs主要富集在细胞周期相关过程、干扰素信号通路和免疫系统过程中，而表达下调的DEGs主要参与细胞外基质的组装/分解、发病机制和细胞粘附。特别地，发现细胞周期和TGF-β信号通路是SMAD 4沉默下改变的经典通路。综上所述，我们的数据揭示了SMAD 4敲低改变了参与卵泡GC发育关键生物学过程的许多基因的表达，并为SMAD 4基因在猪卵泡GC中的作用提供了新的全球线索，从而提高了我们对SMAD 4基因在卵泡发育中的调控机制的理解。
As a key mediator of the transforming growth factor-beta (TGF-β) signaling pathway, which plays a pivotal role in regulating mammalian reproductive performance, Sma- and Mad-related protein 4 (SMAD4) is closely associated with the development of ovarian follicular. However, current knowledge of the genome-wide view on the role of SMAD4 gene in mammalian follicular granulosa cells (GCs) is still largely unknown. In the present study, RNA-Seq was performed to investigate the effects of SMAD4 knockdown by RNA interference (SMAD4-siRNA) in porcine follicular GCs. A total of 1025 differentially expressed genes (DEGs), including 530 upregulated genes and 495 downregulated genes, were identified in SMAD4-siRNA treated GCs compared with that treated with NC-siRNA. Furthermore, functional enrichment analysis indicated that upregulated DEGs in SMAD4-siRNA treated cells were mainly enriched in cell-cycle related processes, interferon signaling pathway, and immune system process, while downregulated DEGs in SMAD4-siRNA treated cells were mainly involved in extracellular matrix organization/disassembly, pathogenesis, and cell adhesion. In particular, cell cycle and TGF-β signaling pathway were discovered as the canonical pathways changed under SMAD4-silencing. Taken together, our data reveals SMAD4 knockdown alters the expression of numerous genes involved in key biological processes of the development of follicular GCs and provides a novel global clue of the role of SMAD4 gene in porcine follicular GCs, thus improving our understanding of regulatory mechanisms of SMAD4 gene in follicular development.