Feng Siyuan, Ma Jideng, Long Keren, Zhang Jinwei, Qiu Wanling, Li Yan, Jin Long, Wang Xun, Jiang Anan, Liu Lingyan, Xiao Weihang, Li Xuewei, Tang Qianzi, Li Mingzhou
Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.
Front Genet. 2020 Jul 31;11:809. doi: 10.3389/fgene.2020.00809. eCollection 2020.
High-altitude acclimatization is a representative example of vertebrates' acclimatization to harsh and extreme environments. Previous studies reported sufficient evidence for a molecular genetic basis of high-altitude acclimatization, and genomic patterns of genetic variation among populations and species have been widely elucidated in recent years. However, understanding of the miRNA role in high-altitude acclimatization have lagged behind, especially in non-model species. To investigate miRNA expression alterations of goats that were induced by high-altitude stress, we performed comparative miRNA transcriptome analysis on six hypoxia-sensitive tissues (heart, kidney, liver, lung, skeletal muscle, and spleen) in two goat populations from distinct altitudes (600 and 3000 m). We obtained the expression value of 1391 mature miRNAs and identified 138 differentially expressed (DE) miRNAs between high and low altitudes. Combined with tissue specificity analysis, we illustrated alterations of expression levels among altitudes and tissues, and found that there were coexisting tissue-specific and -conserved mechanisms for hypoxia acclimatization. Notably, the interplay between DE miRNA and DE target genes strongly indicated post-transcriptional regulation in the hypoxia inducible factor 1, insulin, and p53 signaling pathways, which might play significant roles in high-altitude acclimatization in domestic goats. It's also worth noting that we experimentally confirmed miR-106a-5p to have a negative regulation effect on angiogenesis by directly targeting . These results provide insight into the complicated miRNA expression patterns and regulatory mechanisms of high-altitude acclimatization in domestic goats.
高原适应是脊椎动物适应恶劣极端环境的一个典型例子。以往的研究报告了高原适应分子遗传基础的充分证据，近年来，种群和物种间遗传变异的基因组模式已得到广泛阐明。然而，对miRNA在高原适应中的作用的理解却滞后了，尤其是在非模式物种中。为了研究高原应激诱导的山羊miRNA表达变化，我们对来自不同海拔（600米和3000米）的两个山羊群体的六个低氧敏感组织（心脏、肾脏、肝脏、肺、骨骼肌和脾脏）进行了比较miRNA转录组分析。我们获得了1391个成熟miRNA的表达值，并鉴定出高海拔和低海拔之间有138个差异表达（DE）的miRNA。结合组织特异性分析，我们阐述了海拔和组织间表达水平的变化，发现低氧适应存在组织特异性和保守机制共存的情况。值得注意的是，DE miRNA与DE靶基因之间的相互作用强烈表明在缺氧诱导因子1、胰岛素和p53信号通路中存在转录后调控，这可能在家养山羊的高原适应中发挥重要作用。同样值得注意的是，我们通过实验证实miR-106a-5p通过直接靶向……对血管生成具有负调控作用。这些结果为家养山羊高原适应复杂的miRNA表达模式和调控机制提供了见解。
