Transcriptional response to hypoxia in iPSC-derived endothelial cells from a high altitude adapted population
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PROVIDER: PRJNA1153636 | ENA |
REPOSITORIES: ENA
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Project description:Tibetan adaptation to high-altitude hypoxia remains a classic example of Darwinian selection in humans. Amongst Tibetans, alleles in the EPAS1 gene - whose protein product, Hif-2α, is a central regulator of the hypoxia response - have repeatedly been shown to carry some of the strongest signals of positive selection in humans and to influence several adaptive phenotypes. We recently showed that the selected haplotype at this locus spans a hypoxia-dependent enhancer (ENH5) that contributes to the regulation of EPAS1 in a variety of cell types. However, selective sweep signals alone may account for only part of the phenotypes that differentiate Tibetans from closely related lowlanders. Therefore, there is a pressing need to functionally probe adaptive alleles and their impact at the genome-wide level and across cell types to uncover the full range of beneficial traits. To cast a wider net, we established a library of induced pluripotent stem cells (iPSCs) derived from Tibetan and Han Chinese individuals, a robust model system allowing precise exploration of both locus-specific and genome-wide effects on transcriptional responses. We harness this system by differentiating the iPSC library into vascular endothelium and investigating the locus-specific effects of the ENH5 enhancer in this cellular context. In addition, we use it to explore Tibetan-specific transcriptome-wide responses and find evidence that energy metabolism and immune pathways have been shaped by natural selection in Tibetans. Finally, to aid with the interpretation of the transcriptional differences between populations, we test for polygenic adaptations as a complementary in silico approach for the identification of beneficial Tibetan phenotypes.
2024-12-01 | GSE271457 | GEO
Project description:Tibetan adaptation to high-altitude hypoxia remains a classic example of Darwinian selection in humans. Amongst Tibetans, alleles in the EPAS1 gene - whose protein product, Hif-2α, is a central regulator of the hypoxia response - have repeatedly been shown to carry some of the strongest signals of positive selection in humans and to influence several adaptive phenotypes. We recently showed that the selected haplotype at this locus spans a hypoxia-dependent enhancer (ENH5) that contributes to the regulation of EPAS1 in a variety of cell types. However, selective sweep signals alone may account for only part of the phenotypes that differentiate Tibetans from closely related lowlanders. Therefore, there is a pressing need to functionally probe adaptive alleles and their impact at the genome-wide level and across cell types to uncover the full range of beneficial traits. To cast a wider net, we established a library of induced pluripotent stem cells (iPSCs) derived from Tibetan and Han Chinese individuals, a robust model system allowing precise exploration of both locus-specific and genome-wide effects on transcriptional responses. We harness this system by differentiating the iPSC library into vascular endothelium and investigating the locus-specific effects of the ENH5 enhancer in this cellular context. In addition, we use it to explore Tibetan-specific transcriptome-wide responses and find evidence that energy metabolism and immune pathways have been shaped by natural selection in Tibetans. Finally, to aid with the interpretation of the transcriptional differences between populations, we test for polygenic adaptations as a complementary in silico approach for the identification of beneficial Tibetan phenotypes.
2024-12-01 | GSE271456 | GEO
Project description:Locus-specific and genome-wide analysis of adaptations to hypoxia in iPSC-derived endothelium from a population adapted to high altitude [scRNA-Seq]
| PRJNA1131467 | ENA
Project description:Locus-specific and genome-wide analysis of adaptations to hypoxia in iPSC-derived endothelium from a population adapted to high altitude [RNA-Seq]
| PRJNA1131465 | ENA
Project description:This study evaluates genetic and phenotypic variation in the intermediate altitude Calchaquà population living in the Calchaquà Valleys of the Argentinean Andes in the town of Cachi at 2300 m. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to moderate hypoxia at a intermediate altitude. DNA from 24 saliva samples of CalchaquÃes living at 2300 m in Cachi in the Province of Salta in Argentina was genotyped.
2014-04-05 | E-GEOD-56518 | biostudies-arrayexpress
Project description:This study evaluates genetic and phenotypic variation in the intermediate altitude Calchaquí population living in the Calchaquí Valleys of the Argentinean Andes in the town of Cachi at 2300 m. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to moderate hypoxia at a intermediate altitude.
2014-04-05 | GSE56518 | GEO
Project description:For individuals migrating to or residing permanently at high-altitude regions, environmental hypobaric hypoxia is a primary challenge which induces several physiological or pathological responses. It is well documented that human beings adapt to hypobaric hypoxia via some protective mechanisms, such as erythropoiesis and overproduction of hemoglobin, however little is known on the changes of plasma proteome profiles in accommodation to high-altitude hypobaric hypoxia. In the present study, we investigated differential plasma proteomes of high altitude natives and lowland normal controls by a TMT-based proteomic approach. A total of 818 proteins were identified, of which 137 were differentially altered. Bioinformatics (including GO, KEGG, protein-protein interactions, etc.) analysis revealed the dysregulated proteins were primarily involved in complement and coagulation cascades, anti-oxidative stress and glycolysis. Validations via magnetic Luminex® Assays and ELISA demonstrated that CCL18, C9, PF4, MPO and S100A9 notably up-regulated, and HRG and F11 down-regulated in high altitude natives compared with lowland controls, which were consistent with the proteomic results. Our findings highlight the roles of complement and coagulation cascades, anti-oxidative stress and glycolysis in acclimatization to hypobaric hypoxia and provide a foundation for developing potential diagnostic or/and therapeutic biomarkers for high altitude hypobaric hypoxia-induced diseases.
2019-03-27 | PXD012221 | Pride
Project description:High-altitude adaptation is a representative example of vertebrates getting adapted to harsh and extreme environments. To investigate the miRNA expression alterations of goats that were induced by high altitude stress, we performed comparative miRNA transcriptome analysis on six hypoxia-sensitive tissues (heart, kidney, liver, lung, skeletal muscle and spleen) in two indigenous goat populations from distinct altitudes (600 m and 3000 m). We obtained the expression of 1391 mature miRNAs and identified 138 differentially expressed miRNAs between altitudes. Combined with tissue specificity analysis, we illustrated alterations of expression levels between altitudes and among tissues, which suggested the coexisting tissue-specific and tissue-conserved mechanism for hypoxia adaptation. Notably, the interplay between DE miRNA and DE target genes strongly indicated post-transcriptional regulation in HIF-1 signaling pathway, insulin signaling pathway and p53 signaling pathway, which might play a significant role in high altitude adaptation in domestic goats. These results provide insights into the complicated miRNA expression pattern and regulatory mechanism of high altitude adaptation in domestic goats.
2020-07-23 | GSE125665 | GEO
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
2024-03-16 | GSE261409 | GEO
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.
2017-02-09 | GSE89486 | GEO