Exposomes to Exosomes: Exosomes as Tools to Study Epigenetic Adaptive Mechanisms in High-Altitude Humans

Abstract

Humans on earth inhabit a wide range of environmental conditions and some environments are more challenging for human survival than others. However, many living beings, including humans, have developed adaptive mechanisms to live in such inhospitable, harsh environments. Among different difficult environments, high-altitude living is especially demanding because of diminished partial pressure of oxygen and resulting chronic hypobaric hypoxia. This results in poor blood oxygenation and reduces aerobic oxidative respiration in the mitochondria, leading to increased reactive oxygen species generation and activation of hypoxia-inducible gene expression. Genetic mechanisms in the adaptation to high altitude is well-studied, but there are only limited studies regarding the role of epigenetic mechanisms. The purpose of this review is to understand the epigenetic mechanisms behind high-altitude adaptive and maladaptive phenotypes. Hypobaric hypoxia is a form of cellular hypoxia, which is similar to the one suffered by critically-ill hypoxemia patients. Thus, understanding the adaptive epigenetic signals operating in in high-altitude adjusted indigenous populations may help in therapeutically modulating signaling pathways in hypoxemia patients by copying the most successful epigenotype. In addition, we have summarized the current information about exosomes in hypoxia research and prospects to use them as diagnostic tools to study the epigenome of high-altitude adapted healthy or maladapted individuals.

Identification of blood exosomal metabolomic profiling for high-altitude cerebral edema

“…Metabolites such as adenosine, adenosine 5′-monophosphate, deoxyguanosine 5′-monophosphate, guanosine, and hypoxanthine-9-β-D-arabinofuranoside were found to be significantly decreased. Furthermore, it is well established that hypoxia-induced release of exosomes in tumor cells can significantly impact their secretion, composition, and function, potentially resulting in alterations in the proteins, lipids, and metabolites encapsulated within exosomes 24 , 25 . However, our research findings revealed no significant difference in serum exosome concentrations between the HC group and patients with HACE.…”

Genetic structure and characteristics of Tibetan chickens

“…Still 6 out of 27 selected candidate loci revealed characteristic haplotype markers that were unique genetic identifiers for TBC or even its sub-populations. Given genes RYR2 and CAMK2D were 2 important candidate genes underlying hypoxia adaptation in several species ( Simonson et al, 2010 ; Zhang et al, 2014 ; Wang et al, 2015 ; Wu et al, 2019 ; Padmasekar et al, 2021 ), the nonoverlapped significant selective loci found in different sub-population further suggested that TBC sub-populations had undergone functionally similar adaptations ( Zhu et al, 2018 ). This finding is in line with the recent discovery by The Functional Annotation of Animal Genomes consortium that core set of regulatory elements are functionally conserved, whereas its specific sequence and genomic position are not ( Kern et al, 2021 ).…”

Research Progress on Transorgan Regulation of the Cardiovascular and Motor System through Cardiogenic Exosomes

“…EXOs, as a new research direction and tool, have been applied to the study of epigenetics. For example, Padmasekar et al [ 9 ] used EXOs as tools to study the epigenetic adaptation mechanism of high-altitude humans, and Shrivastava et al [ 10 ] used EXOs as delivery vectors to achieve stable epigenetic inhibition of HIV-1 virus. In addition, EXOs are an important part of the body’s immune response mechanism.…”