■牦牛(Bosgrunniens)是一种重要的牲畜,可以在极寒环境中生存,苛刻,和青藏高原的贫氧条件,并提供肉类,牛奶,以及居住在那里的藏人的交通。然而,推动这种低氧适应的监管网络仍然难以捉摸。
■来自LeiRoqi(LWQY)牦牛及其相关牛(BosTaurus)的心脏组织,这是位于高海拔(HAC)和低海拔(LAC)地区的两个本地牛品种,分别,收集用于RNA测序。在LAC-vs-LWQY和LAC-vs-HAC比较组中,共发现了178个共差异表达的蛋白质编码转录本(co-DES)。包括NFATC2、NFATC1、ENPP2、ACSL4、BAD、和许多其他基因的功能被报道与免疫系统有关,内分泌系统,和脂质代谢。两个和230个lncRNA转录本分别在LAC-vs-LWQY和LAC-vs-HAC比较中差异表达,但没有共差异表达的lncRNA转录本。在共差异表达的58个miRNAs中,18个上调,40个下调。此外,640(501上调和139下调)和152(152上调和一个下调)circRNAs在LAC-vs-LWQY和LAC-vs-HAC比较组中显示差异表达,分别,共有53个上调的共差异表达的circRNAs。多个共同检测,它们是miRNAs/lncRNAs的靶标,显著丰富了与高海拔适应相关的过程,例如,T细胞受体信号传导,VEGF信号,和cAMP信号。通过整合共差异表达的mRNA之间的竞争关系,构建了竞争内源性RNA(ceRNA)网络。miRNA,lncRNAs和circRNAs。此外,构建了低氧适应相关的ceRNA网络,和六个mRNA(MAPKAPK3,PXN,NFATC2,ATP7A,DIAPH1和F2R),八个miRNA(包括miR-195),和15个circRNAs(包括new-circ-017096和new-circ-018073)被认为是调节心脏缺氧适应的新的和有希望的候选者。
■总而言之,本研究中记录的数据提供了对高海拔适应分子网络的新见解,以及涉及该生理过程的蛋白质编码转录本和非编码转录本的更详细信息,这些转录本在高原适应过程中如何相互“串扰”的详细机制值得今后的研究工作。
BACKGROUND: The yak (Bos grunniens) is an important livestock species that can survive the extremely cold, harsh, and oxygen-poor conditions of the Qinghai-Tibetan Plateau and provide meat, milk, and transportation for the Tibetans living there. However, the regulatory network that drive this hypoxic adaptation remain elusive.
RESULTS: The heart tissues from LeiRoqi (LWQY) yak and their related cattle (Bos Taurus) breeds, which are two native cattle breeds located in high altitude (HAC) and low altitude (LAC) regions, respectively, were collected for RNA sequencing. A total of 178 co-differentially expressed protein-coding transcripts (co-DETs) were discovered in each of the LAC-vs-LWQY and LAC-vs-HAC comparison groups, including NFATC2, NFATC1, ENPP2, ACSL4, BAD, and many other genes whose functions were reported to be associated with the immune-system, endocrine-system, and lipid metabolism. Two and 230 lncRNA transcripts were differentially expressed in the LAC-vs-LWQY and LAC-vs-HAC comparisons\' respectively, but no lncRNA transcripts that were co-differentially expressed. Among the 58 miRNAs that were co-differentially expressed, 18 were up-regulated and 40 were down-regulated. In addition, 640 (501 up-regulated and 139 down-regulated) and 152 (152 up-regulated and one down-regulated) circRNAs showed differential expression in LAC-vs-LWQY and LAC-vs-HAC comparison groups, respectively, and 53 up-regulated co-differentially expressed circRNAs were shared. Multiple co-DETs, which are the targets of miRNAs/lncRNAs, are significantly enriched in high-altitude adaptation related processes, such as, T cell receptor signaling, VEGF signaling, and cAMP signaling. A competing endogenous RNA (ceRNA) network was constructed by integrating the competing relationships among co-differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs. Furthermore, the hypoxic adaptation related ceRNA network was constructed, and the six mRNAs (MAPKAPK3, PXN, NFATC2, ATP7A, DIAPH1, and F2R), the eight miRNAs (including miR-195), and 15 circRNAs (including novel-circ-017096 and novel-circ-018073) are proposed as novel and promising candidates for regulation of hypoxic adaptation in the heart.
CONCLUSIONS: In conclusion, the data recorded in the present study provides new insights into the molecular network of high-altitude adaptation along with more detailed information of protein-coding transcripts and non-coding transcripts involved in this physiological process, the detailed mechanisms behind how these transcripts \"crosstalk\" with each other during the plateau adaptation are worthy of future research efforts.