scholarly journals Comparative Analysis of Long Non-Coding RNA and mRNA Expression Provides Insights into Adaptation to Hypoxia in Tibetan Sheep

2020 ◽  
Author(s):  
Jianbin Liu ◽  
Chao Yuan ◽  
Zengkui Lu ◽  
Deqing Zhuoga ◽  
Tingting Guo ◽  
...  
Keyword(s):  
High Altitude ◽  
Expression Profile ◽  
Transcriptome Analysis ◽  
Target Genes ◽  
Genetic Regulation ◽  
Comparative Transcriptome ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Tibetan Sheep ◽  
Hu Sheep

Abstract Background: Tibetan sheep have lived on the Tibetan Plateau for thousands of years and they have a good adaptability to the hypoxic environment and strong disease resistance. However, the molecular mechanism of the Tibetan sheep adapting to this extreme environment, especially the role of genetic regulation is still unknown. Emerging evidence suggests that long non-coding RNAs (lncRNAs) participate in the regulation of a diverse range of biological processes. To explore the potential lncRNAs involved in Tibetan sheep adapting to high altitude hypoxia environment, we analyzed the expression profile of lncRNAs and mRNAs in liver and lung tissue of sheep based on the comparative transcriptome analysis between four Tibetan sheep populations (high altitude) and Hu sheep (low altitude). Results: A total of 7848 differentially expressed (DE) lncRNAs transcripts and 22971 DE mRNAs transcripts were detected by pairwise comparison. The expression patterns of selected mRNAs and lncRNAs were validated by qRT-PCR and the results correlated well with the transcriptome data. Moreover, the functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases showed that DE mRNAs and the target genes of the lncRNAs were significantly enriched in organ morphogenesis, response to stimulus, heme binding, immune system, arginine and proline metabolism, and fatty acid biosynthesis. The prediction of mRNA-mRNA and lncRNA-mRNA interaction networks further revealed transcripts potentially involved in adaptation to high altitude hypoxia, the hub genes that DDX24, PDCD11, EIF4A3, NDUFA11, SART1, PRPF8 and TCONS_00306477, TCONS_00306029, TCONS_00139593, TCONS_00293272, TCONS_00313398 were selected. Additionally, a set of target genes, PIK3R1, IGF1R, FZD6, IFNB2, ATF3, MB, CYP2B4, PSMD13, and TGFB1 were also identified as candidate genes associated with high altitude hypoxia adaptation. Conclusions: A collection of aberrantly expressed lncRNA, a set of target genes and biological pathways known to be relevant for altitude adaptation were identified by comparative transcriptome analysis between Tibetan sheep and Hu sheep. Our results first identified the characterization and expression profile of lncRNAs between Tibetan sheep and Hu sheep and provides insights into the genetic regulation mechanisms for Tibetan sheep adaptation to high altitude hypoxia environments.

scholarly journals Comparative Analysis of Long Non-Coding RNA and mRNA Expression Provides Insights Into Adaptation to Hypoxia in Tibetan Sheep

2021 ◽  
Author(s):  
Fan Wang ◽  
Jianbin Liu ◽  
Qiaoying Zeng ◽  
Deqing Zhuoga
Keyword(s):  
High Altitude ◽  
Expression Profile ◽  
Transcriptome Analysis ◽  
Target Genes ◽  
Genetic Regulation ◽  
Comparative Transcriptome ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Tibetan Sheep ◽  
Hu Sheep

Abstract Tibetan sheep have lived on the Qinghai-Tibetan Plateau for thousands of years and they have a good adaptability to the hypoxic environment and strong disease resistance. However, the molecular mechanism of the Tibetan sheep adapting to this extreme environment, especially the role of genetic regulation is still unknown. Emerging evidence suggests that long non-coding RNAs (lncRNAs) participate in the regulation of a diverse range of biological processes. To explore the potential lncRNAs involved in Tibetan sheep adapting to high altitude hypoxia environment, we analyzed the expression profile of lncRNAs and mRNAs in liver and lung tissue of sheep based on the comparative transcriptome analysis between four Tibetan sheep populations (high altitude) and Hu sheep (low altitude). The results showed a total of 7848 differentially expressed (DE) lncRNAs transcripts and 22971 DE mRNAs transcripts were detected by pairwise comparison. The expression patterns of selected mRNAs and lncRNAs were validated by qRT-PCR and the results correlated well with the transcriptome data. Moreover, the functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases showed that DE mRNAs and the target genes of the lncRNAs were significantly enriched in organ morphogenesis, response to stimulus, heme binding, immune system, arginine and proline metabolism, and fatty acid biosynthesis. The prediction of mRNA-mRNA and lncRNA-mRNA interaction networks further revealed transcripts potentially involved in adaptation to high altitude hypoxia, the hub genes that DDX24, PDCD11, EIF4A3, NDUFA11, SART1, PRPF8 and TCONS_00306477, TCONS_00306029, TCONS_00139593, TCONS_00293272, TCONS_00313398 were selected. Additionally, a set of target genes, PIK3R1, IGF1R, FZD6, IFNB2, ATF3, MB, CYP2B4, PSMD13, and TGFB1 were also identified as candidate genes associated with high altitude hypoxia adaptation. In conclusion, a collection of aberrantly expressed lncRNA, a set of target genes and biological pathways known to be relevant for altitude adaptation were identified by comparative transcriptome analysis between Tibetan sheep and Hu sheep. Our results first identified the characterization and expression profile of lncRNAs between Tibetan sheep and Hu sheep and provides insights into the genetic regulation mechanisms for Tibetan sheep adaptation to high altitude hypoxia environments.

scholarly journals Variations in HIF-1α Contributed to High Altitude Hypoxia Adaptation via Affected Oxygen Metabolism in Tibetan Sheep

Animals ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 58
Author(s):  
Pengfei Zhao ◽  
Zhaohua He ◽  
Qiming Xi ◽  
Hongxian Sun ◽  
Yuzhu Luo ◽  
...  
Keyword(s):  
Tibetan Plateau ◽  
High Altitude ◽  
Genetic Alterations ◽  
The Tibetan Plateau ◽  
Blood Gas ◽  
Altitude Hypoxia ◽  
Merino Sheep ◽  
High Altitude Hypoxia ◽  
Tibetan Sheep ◽  
Hu Sheep

The Tibetan sheep is an indigenous species of the Tibetan plateau and has been well adapted to high-altitude hypoxia. In comparison to lowland sheep breeds, the blood gas indicators have changed and the HIFs signaling pathway is activated in Tibetan sheep. These phenotypic and genetic alterations in Tibetan sheep are thought to be an important basis for adaptation to high-altitude hypoxia and variation in genes encoding the subunits that make up HIFs, such as HIF-1α can affect blood gas indicators. In this study, exons 9, 10, 12 of the HIF-1α gene were sequenced to find variations and 3 SNPs were detected, and these 3 SNPs were genotyped by KASP in 341 Hu sheep and 391 Tibetan sheep. In addition, 197 Hu sheep, 160 Tibetan sheep and 12 Gansu alpine merino sheep were used for blood gas indicators analysis. The results showed significant differences between the blood gas indicators of high-altitude breeds (Tibetan sheep and Gansu alpine merino sheep) and low-altitude breeds (Hu sheep), implying that the differences in blood gas indicators are mainly caused by differences in altitude. The haplotype combinations H2H3 and H1H3 were more frequent in the Tibetan sheep population, H2H3 increases O2 carrying capacity by increasing hematocrit and hemoglobin concentrations; H1H3 makes O2 dissociate more readily from oxyhemoglobin by decreasing partial pressure of oxygen and oxygen saturation. These results suggest that variants at the HIF-1α promote the ability of oxygen utilization in Tibetan sheep, which may underpin the survival and reproduction of Tibetan sheep on the Tibetan plateau.

scholarly journals Integrative plasma proteomic and microRNA analysis of Jersey cattle in response to high-altitude hypoxia

2019 ◽  
Vol 102 (5) ◽  
pp. 4606-4618 ◽  
Author(s):  
Zhiwei Kong ◽  
Chuanshe Zhou ◽  
Bin Li ◽  
Jinzhen Jiao ◽  
Liang Chen ◽  
...  
Keyword(s):  
High Altitude ◽  
Altitude Hypoxia ◽  
Jersey Cattle ◽  
High Altitude Hypoxia

Seeding drug discovery: telomeric tankyrase as a pharmacological target for the pathophysiology of high-altitude hypoxia

2021 ◽  
Author(s):  
Manjula Miglani ◽  
Qadar Pasha ◽  
Archana Gupta ◽  
Anjali Priyadarshini ◽  
Ramendra Pati Pandey ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Altitude ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Pharmacological Target

Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia

2007 ◽  
Vol 292 (3) ◽  
pp. L678-L684 ◽  
Author(s):  
Yuansheng Gao ◽  
Ada D. Portugal ◽  
Sewite Negash ◽  
Weilin Zhou ◽  
Lawrence D. Longo ◽  
...  
Keyword(s):  
High Altitude ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Regulatory Subunit ◽  
Fourth Generation ◽  
Minor Effect ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Rock Activity

An increase in Rho kinase (ROCK) activity is implicated in chronic hypoxia-induced pulmonary hypertension. In the present study, we determined the role of ROCKs in cGMP-dependent protein kinase (PKG)-mediated pulmonary vasodilation of fetal lambs exposed to chronic hypoxia. Fourth generation pulmonary arteries were isolated from near-term fetuses (∼140 days of gestation) delivered from ewes exposed to chronic high altitude hypoxia for ∼110 days and from control ewes. In vessels constricted to endothelin-1, 8-bromoguanosine-cGMP (8-Br-cGMP) caused a smaller relaxation in chronically hypoxic (CH) vessels compared with controls. Rp-8-Br-PET-cGMPS, a PKG inhibitor, attenuated relaxation to 8-Br-cGMP in control vessels to a greater extent than in CH vessels. Y-27632, a ROCK inhibitor, significantly potentiated 8-Br-cGMP-induced relaxation of CH vessels and had only a minor effect in control vessels. The expression of PKG was increased but was not accompanied with an increase in the activity of the enzyme in CH vessels. The expression of type II ROCK and activity of ROCKs were increased in CH vessels. The phosphorylation of threonine (Thr)696 and Thr850 of the regulatory subunit MYPT1 of myosin light chain phosphatase was inhibited by 8-Br-cGMP to a lesser extent in CH vessels than in controls. The difference was eliminated by Y-27632. These results suggest that chronic hypoxia in utero attenuates PKG-mediated relaxation in pulmonary arteries, partly due to inhibition of PKG activity and partly due to enhanced ROCK activity. Increased ROCK activity may inhibit PKG action through increased phosphorylation of MYPT1 at Thr696 and Thr850.

scholarly journals High-altitude hypoxia and preeclampsia

10.2741/2286 ◽  
2007 ◽  
Vol 12 (8-12) ◽  
pp. 2967 ◽  
Author(s):  
Stacy Zamudio
Keyword(s):  
High Altitude ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia

scholarly journals High-altitude hypoxia and periodic breathing during sleep: gender-related differences

2013 ◽  
Vol 22 (3) ◽  
pp. 322-330 ◽  
Author(s):  
Carolina Lombardi ◽  
Paolo Meriggi ◽  
Piergiuseppe Agostoni ◽  
Andrea Faini ◽  
Grzegorz Bilo ◽  
...  
Keyword(s):  
High Altitude ◽  
Periodic Breathing ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia
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