Project description:Acute mountain sickness (AMS) is a common disabling condition in individuals experiencing high altitudes, which may progress to life-threatening high altitude cerebral edema. Today, no established biomarkers are available for prediction of AMS and Non-AMS individuals before exposure to high altitude.MicroRNAs emerge as promising sensitive and specific biomarkers for a variety of diseases. Thus, we sought to identify circulating microRNAs suitable for prediction the susceptible of AMS before exposure to high altitude. A total of 31 microRNAs were differentially expressed between AMS and Non-AMS groups, 15 up-regulated and 16 down-regulated. Up-regulation of miR-369-3p, miR-449b-3p, miR-136-3p, and miR-4791 in patients with AMS compared with Non-AMS individuals were quantitatively confirmed using qPCR (all, P < 0.001). A unique signature encompassing miR-369-3p, miR-449b-3p, and miR-136-3p discriminate AMS from Non-AMS (area under the curve 0.986, 95%CI 0.970-1.000, P < 0.001, LR+: 14.21, LR-: 0.08). This signature yielded a 92.68% sensitivity and a 93.48% specificity for AMS vs. Non-AMS.The study here, for the first time, describes a signature of three circulating microRNAs as a robust biomarker to differentiate AMS from Non-AMS individuals.
Project description:High-altitude polycythemia (HAPC) is a most common chronic mountain sickness, characterized by excessive erythrocytosis caused primarily by persistent arterial hypoxia and ventilatory impairment. It has been a serious public health problem in high-altitude regions. Despite numerous studies on HAPC via genomics, transcriptomics or metabolome approaches, the pathogenesis of HAPC remains largely unclear. Here, we performed single-cell RNA sequencing to reveal the change of transcriptomics profiles of MNC in spleen of mice between HAPC subjects and healthy controls.
Project description:High-altitude polycythemia (HAPC) is a most common chronic mountain sickness, characterized by excessive erythrocytosis caused primarily by persistent arterial hypoxia and ventilatory impairment. It has been a serious public health problem in high-altitude regions. Despite numerous studies on HAPC via genomics, transcriptomics or metabolome approaches, the pathogenesis of HAPC remains largely unclear. Here, we performed single-cell RNA sequencing to reveal the change of transcriptomics profiles of stem progenitor cells and erythrocytes in bone marrow of mice between HAPC subjects and healthy controls.
Project description:Acute mountain sickness (AMS), which may progress to life-threatening high altitude cerebral edema, is a major threat to millions of people who live in or travel to high altitude. Although studies have revealed the risk factors and pathophysiology theories of AMS, the molecular mechanisms of it do not comprehensively illustrate. Here, we used a system-level methodology, RNA sequencing, to explore the molecular mechanisms of AMS at genome-wide level in 10 individuals. After exposure to high altitude, a total of 1,164 and 1,322 differentially expressed transcripts were identified in AMS and non-AMS groups, respectively. Among them, only 328 common transcripts presented between the two groups. Immune and inflammatory responses were overrepresented in participants with AMS, but not in non-AMS individuals. Anti-inflammatory cytokine IL10 and inflammation cytokines IF17F and CCL8 exhibited significantly different genetic connectivity in AMS compared to that of non-AMS individuals based on network analysis. IL10 was down-regulated and both IF17F and CCL8 were un-regulated in AMS individuals. Moreover, the serum concentration of IL10 significantly decreased in AMS patients after exposure to high altitude (p = 0.001) in another population (n=22). There was a large negative correlation between the changes of IL10 concentration, r(22) = -0.52, p = 0.013, and Lake Louise Score. Taken together, our analysis provides unprecedented characterization of AMS transcriptome and identifies that genes involved in immune and inflammatory responses were disturbed in AMS individuals by high altitude exposure. The reduction of IL10 after exposure to high altitude was associated with AMS.
Project description:Altitude acclimatization is the physiological process to restore oxygen delivery to the tissues and promote the oxygen application under high altitude hypoxia. High altitude illness could happen in individuals who did not get acclimatization. Unraveling the molecular underpinnings of altitude acclimatization would help people to understand the beneficial response of body to high altitude hypoxia and disturbed biological process in un-acclimatized individuals. Here, we measured physiological adjustments and circulating microRNAs (cmiRNAs) profiles of individuals exposed to high altitude to explore the altitude acclimatization in humans.
Project description:High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we used sheep as an animal model for low-to-high altitude translocation. We generated multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterized transcriptional changes of all genes in each tissue, and examined multi-tissue temporal dynamics and transcriptional interactions among genes. In particular, we identified critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identified TAD-constrained cis-regulatory elements, which suppressed the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicated that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provided time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals
Project description:Epigenetics may play an important role in the occurrence and development of high-altitude pulmonary edema. To investigate the DNA methylation driving genes associated with high-altitude pulmonary edema, we also performed reduced representation bisulfite sequencing (RRBS) for blood identify differences of DNA methylation status of 10 HAPE patients and 10 healthy volunteers.
Project description:Understanding molecular mechanism associated with high altitude exposure during acclimatization/adaptation/maladaptation. Data reveals specific components of the complex molecular circuitry underlying high altitude pulmonary edema. Individualized outcome prediction were constructed through expression profiling of 39400 genes in sea level sojourners who were acclimatized to high altitude and grouped as controls (n=14), high altitude natives (n=14) and individuals who developed high altitude pulmonary edema within 48-72 hours after air induction to high altitude (n=17).
Project description:Exploratory RNA expression analysis during development of leprosy allows identification of RISK4LEP, a 4-gene blood RNA signature predicting leprosy years before clinical onset.
Project description:Individuals with various high-altitude exposures have been recruited in this study to research the effects of differential exposure to high altitude on the epigenome