Table_1_Meta-analysis of RNA-Seq datasets highlights novel genes/pathways involved in fat deposition in fat-tail of sheep.XLSX

IntroductionFat-tail in sheep is considered as an important energy reservoir to provide energy as a survival buffer during harsh challenges. However, fat-tail is losing its importance in modern sheep industry systems and thin-tailed breeds are more desirable. Using comparative transcriptome analysis to compare fat-tail tissue between fat- and thin-tailed sheep breeds provides a valuable approach to study the complex genetic factors associated with fat-tail development. However, transcriptomic studies often suffer from issues with reproducibility, which can be improved by integrating multiple studies based on a meta-analysis.MethodsHence, for the first time, an RNA-Seq meta-analysis on sheep fat-tail transcriptomes was performed using six publicly available datasets.Results and discussionA total of 500 genes (221 up-regulated, 279 down-regulated) were identified as differentially expressed genes (DEGs). A jackknife sensitivity analysis confirmed the robustness of the DEGs. Moreover, QTL and functional enrichment analysis reinforced the importance of the DEGs in the underlying molecular mechanisms of fat deposition. Protein-protein interactions (PPIs) network analysis revealed the functional interactions among the DEGs and the subsequent sub-network analysis led to identify six functional sub-networks. According to the results of the network analysis, down-regulated DEGs in green and pink sub-networks (like collagen subunits IV, V, and VI, integrins 1 and 2, SCD, SCD5, ELOVL6, ACLY, SLC27A2, and LPIN1) may impair lipolysis or fatty acid oxidation and cause fat accumulation in tail. On the other hand, up-regulated DEGs, especially those are presented in green and pink sub-networks (like IL6, RBP4, LEPR, PAI-1, EPHX1, HSD11B1, and FMO2), might contribute to a network controlling fat accumulation in the tail of sheep breed through mediating adipogenesis and fatty acid biosynthesis. Our results highlighted a set of known and novel genes/pathways associated with fat-tail development, which could improve the understanding of molecular mechanisms behind fat deposition in sheep fat-tail.

绵羊的脂肪尾被视为一种重要的能量储备，能够在严酷的挑战中提供生存缓冲的能源。然而，在现代绵羊产业体系中，脂肪尾的重要性正在逐渐丧失，而细尾品种更受欢迎。通过比较转录组分析，对比脂肪尾和细尾绵羊品种的脂肪尾组织，为研究脂肪尾发育相关的复杂遗传因素提供了一种宝贵的方法。然而，转录组研究常常面临可重复性问题，这一问题可以通过基于荟萃分析整合多个研究得到改善。方法因此，首次对绵羊脂肪尾转录组进行了RNA-Seq荟萃分析，使用了六个公开可用的数据集。结果与讨论共鉴定出500个基因（其中上调基因221个，下调基因279个）作为差异表达基因（DEGs）。刀切敏感性分析证实了DEGs的稳健性。此外，QTL和功能富集分析强化了DEGs在脂肪沉积潜在分子机制中的重要性。蛋白质-蛋白质相互作用（PPIs）网络分析揭示了DEGs之间的功能相互作用，随后通过子网络分析识别出六个功能子网络。根据网络分析的结果，绿色和粉红色子网络（如胶原蛋白亚基IV、V和VI、整合素1和2、SCD、SCD5、ELOVL6、ACLY、SLC27A2和LPIN1）中的下调DEGs可能损害脂解或脂肪酸氧化，导致尾部的脂肪积累。另一方面，上调DEGs，尤其是那些在绿色和粉红色子网络中出现的（如IL6、RBP4、LEPR、PAI-1、EPHX1、HSD11B1和FMO2）可能通过介导脂肪生成和脂肪酸生物合成，有助于控制绵羊品种尾部脂肪积累的网络。我们的研究结果突显了一组与脂肪尾发育相关的已知和新基因/通路，这些结果可能有助于提高对绵羊脂肪尾脂肪沉积背后的分子机制的理解。