Comparison of the Human Transcriptional Response to Three Hypoxic Environments
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE219264 | GEO | 2022/12/05
REPOSITORIES: GEO
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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 exposes humans to hypobaric and hypoxic conditions, which induce various physiological and molecular changes. Recent evidence, mostly from animal models, points towards interaction between circadian rhythms and the hypoxic response, however their human relevance is largely unknown. To examine the interaction between elevated altitude-low oxygen and daily rhythms, we analyzed the effect of different high altitudes in conjunction with day-time on human whole blood transcriptome. We found that high altitude vastly affects the blood transcriptome and unexpectedly, does not necessarily follow a monotonic response to altitude elevation. We observed daily variance in gene expression, which was largely dependent on altitude. Moreover, using digital cytometry approach we estimated the relative changes in abundance of different cell types and found the several immune cell types were responding in a time- and altitude-dependent manner. Taken together, our data shed new light on the transcriptional response to high altitude and its interaction with daily rhythms.
2022-03-03 | GSE196728 | GEO
Project description:Controlled hypobaria presents biology with an environment that is never encountered in terrestrial ecology, yet the apparent components of hypobaria are stresses typical of terrestrial ecosystems. High altitude, for example, presents terrestrial hypobaria always with hypoxia as a component stress, since the relative partial pressure of O2 is constant in the atmosphere. Laboratory-controlled hypobaria, however, allows the dissection of pressure effects away from the effects typically associated with altitude, in particular hypoxia, as the partial pressure of O2 can be varied. In this study, whole transcriptomes of plants grown in ambient (97 kPa/pO2 = 21 kPa) atmospheric conditions were compared to those of plants transferred to five different atmospheres of varying pressure and oxygen composition for 24 h: 50 kPa/pO2 = 10 kPa, 25 kPa/pO2 = 5 kPa, 50 kPa/pO2 = 21 kPa, 25 kPa/pO2 = 21 kPa, or 97 kPa/pO2 = 5 kPa. The plants exposed to these environments were 10 day old Arabidopsis seedlings grown vertically on hydrated nutrient plates. In addition, 5 day old plants were also exposed for 24 h to the 50 kPa and ambient environments to evaluate age-dependent responses. The gene expression profiles from roots and shoots showed that the hypobaric response contained more complex gene regulation than simple hypoxia, and that adding back oxygen to normoxic conditions did not completely alleviate gene expression changes in hypobaric responses.
2017-05-11 | GSE87868 | GEO
Project description:Controlled hypobaria presents biology with an environment that is never encountered in terrestrial ecology, yet the apparent components of hypobaria are stresses typical of terrestrial ecosystems. High altitude, for example, presents terrestrial hypobaria always with hypoxia as a component stress, since the relative partial pressure of O2 is constant in the atmosphere. Laboratory-controlled hypobaria, however, allows the dissection of pressure effects away from the effects typically associated with altitude, in particular hypoxia, as the partial pressure of O2 can be varied. In this study, whole transcriptomes of plants grown in ambient (97 kPa/pO2 = 21 kPa) atmospheric conditions were compared to those of plants transferred to five different atmospheres of varying pressure and oxygen composition for 24 h: 50 kPa/pO2 = 10 kPa, 25 kPa/pO2 = 5 kPa, 50 kPa/pO2 = 21 kPa, 25 kPa/pO2 = 21 kPa, or 97 kPa/pO2 = 5 kPa. The plants exposed to these environments were 10 day old Arabidopsis seedlings grown vertically on hydrated nutrient plates. In addition, 5 day old plants were also exposed for 24 h to the 50 kPa and ambient environments to evaluate age-dependent responses. The gene expression profiles from roots and shoots showed that the hypobaric response contained more complex gene regulation than simple hypoxia, and that adding back oxygen to normoxic conditions did not completely alleviate gene expression changes in hypobaric responses.
2017-05-11 | GSE87867 | 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
Project description:In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. Overall design: Adults wild type and dystrophic flies (3-5 days old) were exposed to hypobaric hypoxia for two weeks during the summer expedition to Mount McKinley, Alaska (6194 MASL). Another set of wild types and dystrophic flies were exposed to normobaric hypoxia according to the table I obtained during the climbing expedition. During the expedition, the flies were maintained in vials with regular molasses and covered by thermo isolation to avoid low temperature, keeping the temperature at 25C. The experiment performed in the laboratory also used vials with regular molasses and at 25C. Table I. Expedition log book for mount McKinley ascent. Information obtained during the ascent and summit of Mount McKinley, June 1st to June 16th of 2007. The oxygen pressure (PO2) was calculated from the barometric pressure. GNB means go and back from the mentioned point. DAY In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. Overall design: Adults wild type and dystrophic flies (3-5 days old) were exposed to hypobaric hypoxia for two weeks during the summer expedition to Mount McKinley, Alaska (6194 MASL). Another set of wild types and dystrophic flies were exposed to normobaric hypoxia according to the table I obtained during the climbing expedition. During the expedition, the flies were maintained in vials with regular molasses and covered by thermo isolation to avoid low temperature, keeping the temperature at 25C. The experiment performed in the laboratory also used vials with regular molasses and at 25C. Table I. Expedition log book for mount McKinley ascent. Information obtained during the ascent and summit of Mount McKinley, June 1st to June 16th of 2007. The oxygen pressure (PO2) was calculated from the barometric pressure. GNB means go and back from the mentioned point. DAY LOCATION ALTITUDE m PO2 mmHg (%) 1 Base Camp 2200 123.6 (16.3%) 2 Base Camp 2200 123.6 (16.3%) 3 Base Camp 2200 123.6 (16.3%) 4 Ski Hill 2400 120.7 (15.9%) 5 Kahiltna Pass 2950 113.0 (14.9%) 6 Motorcycle Hill 3350 107.7 (14.2%) 7 Motorcycle Hill 3350 107.7 (14.2%) 8 GNB from Motorcycle 4150 (5 hours) 97.7 (12.9%) 9 Medical Camp 4350 95.3 (12.5%) 10 GNB from Medical Camp 4150 (5 hours) 97.7 (12.9%) 11 Medical Camp 4350 95.3 (12.5%) 12 GNB from Medical Camp 4900 89.0 (11.7%) 13 Medical Camp 4350 95.3 (12.5%) 14 High Camp 5250 85.1 (11.2%) 15 Summit 6194 (0.3 hours) 75.4 (9.9%) 16 High Camp 5250 85.1 (11.2%)
2010-07-31 | E-GEOD-15879 | biostudies-arrayexpress
Project description:This study evaluates genetic and phenotypic variation in the high altitude Colla population living in the Argentinean Andes above 3500 m. They were compared to the Wichí population living in the nearby lowlands of the Gran Chaco region. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to hypobaric hypoxia. We have genotyped 25 individuals from both populations for 730,525 SNPs.
2014-02-20 | GSE55175 | GEO
Project description:Extreme hypobaria is a novel abiotic stress that is outside the evolutionary experience of terrestrial plants. In natural environments, the practical limit of atmospheric pressure experienced by higher plants is about 50 kPa or ~.5 atmospheres; a limit that is primarily imposed by the combined stresses inherent to high altitude conditions of terrestrial mountains. However, in highly controlled chambers and within extra-terrestrial greenhouses the atmospheric pressure component can be isolated from other high altitude stresses such as temperature, desiccation, and even hypoxia. In addition, hypobaria can be carried to extremes beyond what is possible in terrestrial biomes, and explored as a single variable in the examination of plant responses to novel stress. Previous studies have shown that plants adjust to hypobaric stress by differentially expressing suites of genes in unique combinations that are not equal to the dissected components of hypobaric stress (such as hypoxia and desiccation). Here we examine the organ-specific progression of transcriptional strategies for physiological adaptation to hypobaric stress over time. An abrupt transition from a near-sea level pressure of 97 kPa to only 5 kPa is accompanied by the differential expression of hundreds of genes. However, the transcriptomic reaction to hypobaric conditions lying between these two extremes reveals complex, organ-specific responses that vary over a time course of hypobaric exposure, and that are also not linear with respect to a simple gradient of severity. It is also clear that plants adjust over time such that the gene expression patterns that are initially elicited to cope with hypobaria are mediated as plants adjust their metabolism to this environment. The patterns of genome-wide changes in gene expression across a gradient of atmospheric pressures, and over a time course of several days allows for the development of theories of how plant metabolisms may be adapting to changes in atmospheric pressures.
2017-05-11 | GSE87904 | GEO
Project description:Extreme hypobaria is a novel abiotic stress that is outside the evolutionary experience of terrestrial plants. In natural environments, the practical limit of atmospheric pressure experienced by higher plants is about 50 kPa or ~.5 atmospheres; a limit that is primarily imposed by the combined stresses inherent to high altitude conditions of terrestrial mountains. However, in highly controlled chambers and within extra-terrestrial greenhouses the atmospheric pressure component can be isolated from other high altitude stresses such as temperature, desiccation, and even hypoxia. In addition, hypobaria can be carried to extremes beyond what is possible in terrestrial biomes, and explored as a single variable in the examination of plant responses to novel stress. Previous studies have shown that plants adjust to hypobaric stress by differentially expressing suites of genes in unique combinations that are not equal to the dissected components of hypobaric stress (such as hypoxia and desiccation). Here we examine the organ-specific progression of transcriptional strategies for physiological adaptation to hypobaric stress over time. An abrupt transition from a near-sea level pressure of 97 kPa to only 5 kPa is accompanied by the differential expression of hundreds of genes. However, the transcriptomic reaction to hypobaric conditions lying between these two extremes reveals complex, organ-specific responses that vary over a time course of hypobaric exposure, and that are also not linear with respect to a simple gradient of severity. It is also clear that plants adjust over time such that the gene expression patterns that are initially elicited to cope with hypobaria are mediated as plants adjust their metabolism to this environment. The patterns of genome-wide changes in gene expression across a gradient of atmospheric pressures, and over a time course of several days allows for the development of theories of how plant metabolisms may be adapting to changes in atmospheric pressures.
2017-05-11 | GSE87903 | GEO
Project description:This study evaluates genetic and phenotypic variation in the high altitude Colla population living in the Argentinean Andes above 3500 m. They were compared to the Wichà population living in the nearby lowlands of the Gran Chaco region. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to hypobaric hypoxia. We have genotyped 25 individuals from both populations for 730,525 SNPs. DNA from 25 saliva samples from Collas living >3500 m and 25 saliva samples from Wichà living <500 m from the Province of Salta in Argentina was genotyped
2014-02-20 | E-GEOD-55175 | biostudies-arrayexpress