Table_3_Comparative microRNA Transcriptomes in Domestic Goats Reveal Acclimatization to High Altitude.xlsx

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 FLT-1. 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应对严苛极端环境的典型适应范例。过往研究已为高原适应的分子遗传基础提供了充分证据，近年来种群与物种间遗传变异的基因组模式也已得到广泛阐明。然而，目前对微小RNA（miRNA）在高原适应中所发挥作用的认知仍相对滞后，在非模式生物中尤为突出。为探究高原胁迫诱导的山羊miRNA表达变化，本研究对来自不同海拔（600米与3000米）的两个山羊种群的6种缺氧敏感组织（心脏、肾脏、肝脏、肺脏、骨骼肌与脾脏）开展了比较miRNA转录组分析。本研究获得了1391个成熟miRNA的表达量数据，并鉴定出高低海拔种群间存在138个差异表达（DE）miRNA。结合组织特异性分析，本研究阐明了不同海拔与组织间的表达水平变化，并发现缺氧适应同时存在组织特异性与保守性调控机制。值得注意的是，差异表达miRNA与差异表达靶基因的互作分析强烈表明，缺氧诱导因子1（hypoxia inducible factor 1）、胰岛素及p53信号通路存在转录后调控，这些通路可能在家山羊高原适应中发挥关键作用。此外，本研究通过实验证实，miR-106a-5p可通过直接靶向FLT-1对血管生成产生负调控作用。本研究结果为家山羊高原适应中复杂的miRNA表达模式及调控机制提供了新的见解。