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. 2020 Sep 8:11:559074.
doi: 10.3389/fgene.2020.559074. eCollection 2020.

Transcriptomic Changes in Young Japanese Males After Exposure to Acute Hypobaric Hypoxia

Yoshiki Yasukochi  1 , Sora Shin  2 , Hitoshi Wakabayashi  3 , Takafumi Maeda  4   5
Affiliations

Transcriptomic Changes in Young Japanese Males After Exposure to Acute Hypobaric Hypoxia

Yoshiki Yasukochi et al. Front Genet. .

Abstract

After the genomic era, the development of high-throughput sequencing technologies has allowed us to advance our understanding of genetic variants responsible for adaptation to high altitude in humans. However, transcriptomic characteristics associated with phenotypic plasticity conferring tolerance to acute hypobaric hypoxic stress remain unclear. To elucidate the effects of hypobaric hypoxic stress on transcriptional variability, we aimed to describe transcriptomic profiles in response to acute hypobaric hypoxia in humans. In a hypobaric hypoxic chamber, young Japanese males were exposed to a barometric pressure of 493 mmHg (hypobaric hypoxia) for 75 min after resting for 30 min at the pressure of 760 mmHg (normobaric normoxia) at 28°C. Saliva samples of the subjects were collected before and after hypobaric hypoxia exposure, to be used for RNA sequencing. Differential gene expression analysis identified 30 significantly upregulated genes and some of these genes may be involved in biological processes influencing hematological or immunological responses to hypobaric hypoxic stress. We also confirmed the absence of any significant transcriptional fluctuations in the analysis of basal transcriptomic profiles under no-stimulus conditions, suggesting that the 30 genes were actually upregulated by hypobaric hypoxia exposure. In conclusion, our findings showed that the transcriptional profiles of Japanese individuals can be rapidly changed as a result of acute hypobaric hypoxia, and this change may influence the phenotypic plasticity of lowland individuals for acclimatization to a hypobaric hypoxic environment. Therefore, the results obtained in this study shed light on the transcriptional mechanisms underlying high-altitude acclimatization in humans.

Keywords: RNA-seq; acclimatization; differentially expressed gene; hypobaric hypoxia; saliva; transcriptome.

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Figures

FIGURE 1
FIGURE 1
Transcriptome similarity among samples from three Japanese subjects participating in the acute hypobaric hypoxic experiments. (A) Principal component analysis of RNA-seq data plotted according to the first (horizontal axis) and second (vertical axis) principal components. (B) Heatmap of Euclidean distance between the expression vectors. The Euclidean distance was calculated using the R dist function.
FIGURE 2
FIGURE 2
Expression levels of the top 10 differentially expressed genes in each of the study subjects. Read counts represent the estimated expression abundance at the gene level.
FIGURE 3
FIGURE 3
Network analysis for differentially expressed genes (DEGs), with the exception of long non-coding RNA or processed transcript, identified in the present study (closed black circles) with the use of GeneMANIA ver. 3.5.1 Cytoscape plugin via Cytoscape ver. 3.7.1. Interactions between the DEGs are indicated by bold lines. Genes represented by gray circles are putative mediators of the interactions between DEGs.
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