Transcriptomic and epigenomic profiles analysis during human acclimatization to simulated high-altitude hypoxia
Abstract
Hypobaric hypoxia (HH) induces coordinated physiological and molecular responses supporting acclimatization to reduced oxygen availability. However, the temporal integration of blood mRNA and miRNA expression during early HH exposure remains incompletely understood. Eight healthy males were exposed for 72 h to simulated moderate HH (~ 3500 m) in the terraXcube facility. Blood transcriptomic and miRNA profiles were analyzed at baseline and after 12, 24, and 72 h, together with physiological variables, reactive oxygen species (ROS), and circulating inflammatory and endothelial biomarkers. Differential expression analysis revealed a progression from early stress and innate immune responses at 12 h, involving FOSB , CITED4 , and IDO1 , to remodeling of lymphocyte-specific programs at 24 h, including PAX5 , TCF7 , and TNFRSF13C . At 72 h, broader changes involved AP-1 components ( JUN , JUNB , and FOSB ), lymphocyte regulators ( PAX5 and FOXP3 ), and the antioxidant gene SOD2 . Integrated analysis identified predicted miRNA–mRNA pairs displaying inverse expression patterns within these pathways. Notably, miR-486-3p was consistently upregulated and miR-29c-5p downregulated across all time points. Plasma biomarkers remained largely stable, except for a transient increase in ICAM-1 and a marked decrease in TNF-α at 12 h, while ROS increased early and subsequently stabilized. Together, these findings identify distinct but overlapping phases of early HH acclimatization, progressing from stress and innate immune activation to lymphocyte-specific and redox remodeling. The temporal dissociation between coordinated mRNA and miRNA expression changes and limited circulating inflammatory responses indicates that molecular adaptation extends beyond detectable systemic inflammatory activation.
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BibTeX
@article{giannella2026transcriptomic,
title = {{Transcriptomic and epigenomic profiles analysis during human acclimatization to simulated high-altitude hypoxia}},
author = {Alessandra Giannella and Simona Mrakic-Sposta and Alessandra Vezzoli and Arianna Magrini and Lara Favero and Laura Rigon and Narjis Khatoon and Giacomo Strapazzon and Hannes Gatterer and Christoph Siebenmann and Maja Schlittler and Giulio Ceolotto and Sandro Malacrida},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-73659-5},
url = {https://www.nature.com/articles/s41598-026-73659-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transcriptomic and epigenomic profiles analysis during human acclimatization to simulated high-altitude hypoxia
AU - Alessandra Giannella
AU - Simona Mrakic-Sposta
AU - Alessandra Vezzoli
AU - Arianna Magrini
AU - Lara Favero
AU - Laura Rigon
AU - Narjis Khatoon
AU - Giacomo Strapazzon
AU - Hannes Gatterer
AU - Christoph Siebenmann
AU - Maja Schlittler
AU - Giulio Ceolotto
AU - Sandro Malacrida
PY - 2026
DA - 2026/10/02
JO - Scientific Reports
DO - 10.1038/s41598-026-73659-5
UR - https://www.nature.com/articles/s41598-026-73659-5
AB - Hypobaric hypoxia (HH) induces coordinated physiological and molecular responses supporting acclimatization to reduced oxygen availability. However, the temporal integration of blood mRNA and miRNA expression during early HH exposure remains incompletely understood. Eight healthy males were exposed for 72 h to simulated moderate HH (~ 3500 m) in the terraXcube facility. Blood transcriptomic and miRNA profiles were analyzed at baseline and after 12, 24, and 72 h, together with physiological variables, reactive oxygen species (ROS), and circulating inflammatory and endothelial biomarkers. Differential expression analysis revealed a progression from early stress and innate immune responses at 12 h, involving FOSB , CITED4 , and IDO1 , to remodeling of lymphocyte-specific programs at 24 h, including PAX5 , TCF7 , and TNFRSF13C . At 72 h, broader changes involved AP-1 components ( JUN , JUNB , and FOSB ), lymphocyte regulators ( PAX5 and FOXP3 ), and the antioxidant gene SOD2 . Integrated analysis identified predicted miRNA–mRNA pairs displaying inverse expression patterns within these pathways. Notably, miR-486-3p was consistently upregulated and miR-29c-5p downregulated across all time points. Plasma biomarkers remained largely stable, except for a transient increase in ICAM-1 and a marked decrease in TNF-α at 12 h, while ROS increased early and subsequently stabilized. Together, these findings identify distinct but overlapping phases of early HH acclimatization, progressing from stress and innate immune activation to lymphocyte-specific and redox remodeling. The temporal dissociation between coordinated mRNA and miRNA expression changes and limited circulating inflammatory responses indicates that molecular adaptation extends beyond detectable systemic inflammatory activation.
SN - 2045-2322
ER -