Temporal transcriptome analysis suggest modulation of multiple pathways and gene network involved in cell-cell interaction during early phase of high altitude exposure

Abstract

High altitude (HA) conditions induce several physiological and molecular changes, prevalent in individuals who are unexposed to this environment. Individuals exposed towards HA hypoxia yields physiological and molecular orchestration to maintain adequate tissue oxygen delivery and supply at altitude. This study aimed to understand the temporal changes at altitude of 4,111m. Physiological parameters and transcriptome study was conducted at high altitude day 3, 7, 14 and 21. We observed changes in differentially expressed gene (DEG) at high altitude time points along with altered BP, HR, SpO 2 , mPAP. Physiological changes and unsupervised learning of DEG's discloses high altitude day 3 as distinct time point. Gene enrichment analysis of ontologies and pathways indicate cellular dynamics and immune response involvement in early day exposure and later stable response. Major clustering of genes involved in cellular dynamics deployed into broad categories: cell-cell interaction, blood signaling, coagulation system, and cellular process. Our data reveals genes and pathways perturbed for conditions like vascular remodeling, cellular homeostasis. In this study we found the nodal point of the gene interactive network and candidate gene controlling many cellular interactive pathways VIM, CORO1A, CD37, STMN1, RHOC, PDE7B, NELL1, NRP1 and TAGLN and the most significant among them i.e. VIM gene was identified as top hub gene. This study suggests a unique physiological and molecular perturbation likely to play a critical role in high altitude associated pathophysiological condition during early exposure compared to later time points.

Comparative Transcriptome Analyses of Gayal (Bos frontalis), Yak (Bos grunniens), and Cattle (Bos taurus) Reveal the High-Altitude Adaptation

“…Increasing evidence shows that the harsh environment of hypoxia may regulate the immune system ( Mishra and Ganju, 2010 ; Gaur et al, 2020 ). In the present study, we found that the immune system of the spleen in gayal and yak was highly regulated.…”

Genomic Variation, Population History, and Long-Term Genetic Adaptation to High Altitudes in Tibetan Partridge (Perdix hodgsoniae)

“…GRIK2 (glutamate ionotropic receptor kainate type subunit 2) is a neurotransmitter receptor activated in a variety of normal neurophysiologic processes ( Sayers et al 2022 ) and acts as a thermoreceptor conferring sensitivity to cold temperatures ( The UniProt Consortium 2021 ). GRIK2 has been previously identified as a candidate gene associated with high-altitude adaptation in humans and other animals ( Ai et al 2014 ; Foll et al 2014 ; Gaur et al 2020 ). Together with ESR1 , these additional genes are possible candidate genes associated with high-altitude adaptation in Tibetan Partridges.…”

The human blood transcriptome exhibits time-of-day-dependent response to hypoxia: Lessons from the highest city in the world

“…The blood plays a pivotal role in this response, primarily given its principal role as an oxygen carrier but also due to its other roles (e.g., coagulation, immune, and endocrine signaling). Few studies in the past investigated the blood transcriptional response to high altitude in humans ( Chen et al., 2012 ; Gaur et al., 2020 ; Liu et al., 2017 ). The current study has several important advantages compared with previous works.…”