202 Longitudinal comparative transcriptomics of dairy cattle at different altitudes reveals unique mechanisms underlying plateau hypoxia adaptation

Abstract The adaptation of livestock to high altitude hypoxic environment (plateau hypoxia adaptation) is important as they have a key role in the socio-economic conditions of the local residents. However, the underlying molecular mechanisms of plateau hypoxia adaptation of livestock are poorly understood. This study was objective to 1) construct the longitudinal transcriptional profiles of dairy cattle across five development stages; 2) reveal the transcriptomic changes of peripheral blood under different altitudes environment; and 3) identify key genes involved in plateau hypoxia adaptation in bovine. In this study, 109 peripheral blood samples from 70 Holstein cattle were performed whole transcriptome sequencing, including 56 at high altitude (> 3600 m) at five development stages (1, 2, 6, 12 and 18 mo) from 56 individuals, and 53 at low altitude (~1000 m) at three development stages (1, 2 and 6 mo) from 14 individuals. The peripheral transcriptional profile was obtained for high altitude cattle at five development stages, and for low altitude cattle for three development stages. By the transcriptome profile analysis in plateau cattle across five development stages, it was found that there were significant differences on mRNA transcriptome at different stages, and a noticeable shift occurred between 2 mo and 6 mo. By a comparative analysis of the transcription levels between high and low altitude cattle, 795, 900 and 880 differentially expressed genes (DEGs) were identified at the age of 1, 2 and 6 mo, respectively. The DEGs at three stages were enriched in several cellular communication, hypoxia response, and regulation of blood pressure, and immune-related signaling pathways. Furthermore, there were 64 DEGs shared across three comparative analyses at the three stages. By functional annotation analysis, we observed the shared DEGs of the three stages were enriched in the Notch signaling involved in heart development, regulation of phosphorylation, and positive regulation of MAP kinase activity. In summary, this study revealed the development-related transcriptomic shifts from birth to 18 mo of age in dairy cattle, and preliminarily elucidated the important signaling pathways involved in bovine plateau hypoxia adaptation by comparative analysis between high and low altitude cattle. The results of the current study will drive a better understanding of plateau hypoxia adaptation and can provide molecular targets for future breeding of plateau-adapted dairy cattle.