Department of Animal Sciences, Auburn University, 559 Devall Dr, Auburn, AL, 36849, USA.
BMC Genomics. 2018 May 10;19(1):351. doi: 10.1186/s12864-018-4738-2.
The maturation and successful acquisition of developmental competence by an oocyte, the female gamete, during folliculogenesis is highly dependent on molecular interactions with somatic cells. Most of the cellular interactions identified, thus far, are modulated by growth factors, ions or metabolites. We hypothesized that this interaction is also modulated at the transcriptional level, which leads to the formation of gene regulatory networks between the oocyte and cumulus cells. We tested this hypothesis by analyzing transcriptome data from single oocytes and the surrounding cumulus cells collected from antral follicles employing an analytical framework to determine interdependencies at the transcript level.
We overlapped our transcriptome data with putative protein-protein interactions and identified hundreds of ligand-receptor pairs that can transduce paracrine signaling between an oocyte and cumulus cells. We determined that 499 ligand-encoding genes expressed in oocytes and cumulus cells are functionally associated with transcription regulation (FDR < 0.05). Ligand-encoding genes with specific expression in oocytes or cumulus cells were enriched for biological functions that are likely associated with the coordinated formation of transzonal projections from cumulus cells that reach the oocyte's membrane. Thousands of gene pairs exhibit significant linear co-expression (absolute correlation > 0.85, FDR < 1.8 × 10) patterns between oocytes and cumulus cells. Hundreds of co-expressing genes showed clustering patterns associated with biological functions (FDR < 0.5) necessary for a coordinated function between the oocyte and cumulus cells during folliculogenesis (i.e. regulation of transcription, translation, apoptosis, cell differentiation and transport).
Our analyses revealed a complex and functional gene regulatory circuit between the oocyte and surrounding cumulus cells. The regulatory profile of each cumulus-oocyte complex is likely associated with the oocytes' developmental potential to derive an embryo.
卵子是雌性配子，在卵泡发生过程中其成熟和成功获得发育能力高度依赖于与体细胞的分子相互作用。迄今为止，大多数已鉴定的细胞相互作用都是由生长因子、离子或代谢物调节的。我们假设这种相互作用也在转录水平上受到调节，这导致卵母细胞和颗粒细胞之间形成基因调控网络。我们通过分析来自窦卵泡的单个卵母细胞和周围颗粒细胞的转录组数据来检验这一假设，采用分析框架确定转录水平上的相互依赖关系。
我们将转录组数据与假定的蛋白质-蛋白质相互作用重叠，并鉴定了数百个配体-受体对，可以在卵母细胞和颗粒细胞之间传递旁分泌信号。我们确定了在卵母细胞和颗粒细胞中表达的 499 个配体编码基因与转录调节功能相关（FDR<0.05）。在卵母细胞或颗粒细胞中特异性表达的配体编码基因富集了与协调形成从颗粒细胞延伸到卵母细胞膜的透明带突起相关的生物学功能。数千个基因对在卵母细胞和颗粒细胞之间表现出显著的线性共表达（绝对相关系数>0.85，FDR<1.8×10）模式。数百个共表达基因显示出与生物学功能相关的聚类模式（FDR<0.5），这些功能对于卵母细胞和颗粒细胞在卵泡发生过程中的协调功能（即转录、翻译、细胞凋亡、细胞分化和运输的调节）是必要的。
我们的分析揭示了卵母细胞和周围颗粒细胞之间复杂而功能性的基因调控回路。每个卵母细胞-颗粒细胞复合体的调节谱可能与卵母细胞的发育潜力有关，以产生胚胎。
