Physiology and Transcriptomics Analysis Reveal the Contribution of Lungs on High-Altitude Hypoxia Adaptation in Tibetan Sheep

Zhao, Pengfei; Zhao, Fangfang; Hu, Jiang; Wang, Jiqing; Liu, Xiu; Zhao, Zhidong; Xi, Qiming; Sun, Hongxian; Li, Shaobin; Luo, Yuzhu

doi:10.3389/fphys.2022.885444

Cited by 4 publications

(3 citation statements)

References 63 publications

(67 reference statements)

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“…In addition to the genes related to early domestication, a panel of interesting genes associated with other economic traits was also revealed. These genes were previously reported in goats, sheep and other species, showing correlations with spermatogenesis and sperm motility ( KIF3B , KIF17 , KIAA0825 and TNFRSF21 ) [ 53 , 54 , 55 , 56 ], growth and development ( TNPO2 , IFT80 , UCP2 , UCP3 , GHRHR , SIM1 , CCM2L , CTNNA3 and CTNNA1 ) [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ], fat deposition ( ACSF3 and FGGY ) [ 65 , 66 ], chicken heat tolerance ( TSHR and SUGCT ) [ 67 ], high-altitude hypoxia adaptation ( CHL1 ) [ 68 ], milk composition ( GHRHR ) [ 69 ], milk flavour ( ACSF3 ) [ 70 ], carcass traits ( GHRHR ) [ 71 ] and hair follicle morphogenesis ( GLI2 ) [ 72 ]. The iHS and ROH methods both detected some genes, but each method found additional genes not detected by the other.…”

Section: Discussionmentioning

confidence: 99%

Identifying Candidate Genes for Litter Size and Three Morphological Traits in Youzhou Dark Goats Based on Genome-Wide SNP Markers

Sun,

Niu,

Jiang

et al. 2023

Genes

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This study aimed to reveal the potential genetic basis for litter size, coat colour, black middorsal stripe and skin colour by combining genome-wide association analysis (GWAS) and selection signature analysis and ROH detection within the Youzhou dark (YZD) goat population (n = 206) using the Illumina GoatSNP54 BeadChip. In the GWAS, we identified one SNP (snp54094-scaffold824-899720) on chromosome 11 for litter size, two SNPs on chromosome 26 (snp11508-scaffold142-1990450, SORCS3) and chromosome 12 (snp55048-scaffold842-324525, LOC102187779) for coat colour and one SNP on chromosome 18 (snp56013-scaffold873-22716, TCF25) for the black middorsal stripe. In contrast, no SNPs were identified for skin colour. In selection signature analysis, 295 significant iHS genomic regions with a mean |iHS| score > 2.66, containing selection signatures encompassing 232 candidate genes were detected. In particular, 43 GO terms and one KEGG pathway were significantly enriched in the selected genes, which may contribute to the excellent environmental adaptability and characteristic trait formation during the domestication of YZD goats. In ROH detection, we identified 4446 ROH segments and 282 consensus ROH regions, among which nine common genes overlapped with those detected using the iHS method. Some known candidate genes for economic traits such as reproduction (TSHR, ANGPT4, CENPF, PIBF1, DACH1, DIS3, CHST1, COL4A1, PRKD1 and DNMT3B) and development and growth (TNPO2, IFT80, UCP2, UCP3, GHRHR, SIM1, CCM2L, CTNNA3 and CTNNA1) were revealed by iHS and ROH detection. Overall, this study is limited by the small population size, which affects the results of GWAS to a certain extent. Nevertheless, our findings could provide the first overview of the genetic mechanism underlying these important traits and provide novel insights into the future conservation and utilisation of Chinese goat germplasm resources.

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Section: Discussionmentioning

confidence: 99%

Identifying Candidate Genes for Litter Size and Three Morphological Traits in Youzhou Dark Goats Based on Genome-Wide SNP Markers

Sun,

Niu,

Jiang

et al. 2023

Genes

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“…In a study involving pulmonary adaption to hypoxia at high altitude, Chl1 was one of the most downregulated genes, possibly modulating the enhanced ventilatory response after exposure to hypoxia. [ 78 ] These target genes are expressed in the airway epithelium, basal cells, and PNECs as shown from the LungMAP database. Furthermore, ISH studies from this study localized miR-30a in the bronchioles.…”

Section: Discussionmentioning

confidence: 99%

Loss of microRNA-30a and sex-specific effects on the neonatal hyperoxic lung injury

et al. 2023

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Background Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions. Methods Wild-type and miR-30a−/− neonatal mice were exposed to hyperoxia [95% FiO2, postnatal day [PND1-5] or room air before being euthanized on PND21. Alveolarization, pulmonary microvascular development, differences in lung transcriptome, and miR-30a expression were assessed in lungs from WT and miR-30a−/− mice of either sex. Blood transcriptomic signatures from preterm newborns (with and without BPD) were correlated with WT and miR-30a−/− male and female lung transcriptome data. Results Significantly, the sex-specific differences observed in WT mice were abrogated in the miR-30a−/− mice upon exposure to hyperoxia. The loss of miR-30a expression eliminated the protective effect in females, suggesting that miR-30a plays an essential role in regulating alveolarization and angiogenesis. Transcriptome analysis by whole lung RNA-Seq revealed a significant response in the miR-30a−/− female hyperoxia-exposed lung, with enrichment of pathways related to cell cycle and neuroactive ligand–receptor interaction. Gene expression signature in the miR-30a−/− female lung associated with human BPD blood transcriptomes. Finally, we showed the spatial localization of miR-30a transcripts in the bronchiolar epithelium. Conclusions miR-30a could be one of the biological factors mediating the resilience of the female preterm lung to neonatal hyperoxic lung injury. A better understanding of the effects of miR-30a on pulmonary angiogenesis and alveolarization may lead to novel therapeutics for treating BPD.

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“…This may be closely related to the adaptation of yaks to the hypoxic environment of the plateau and reduces water consumption during respiration. At the same time, studies have shown that abundant dilated capillaries and large numbers of erythrocytes in the alveolar septa are conducive to increased alveolar ventilation and oxygen transport [51][52][53][54][55][56]. We measured the percentage of alveolar septa at all levels of the peribronchiolar alveoli in yaks after H&E, Masson, and PAS staining, observing a highly significant difference compared to that of cattle, and we also observed that the alveolar septa in yaks between adjacent alveoli was rich in capillaries, and that the number of red blood cells was higher than that of cattle.…”

Section: Discussionmentioning

confidence: 99%

Study of Transcriptomic Analysis of Yak (Bos grunniens) and Cattle (Bos taurus) Pulmonary Artery Smooth Muscle Cells under Oxygen Concentration Gradients and Differences in Their Lung Histology and Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors

Zhang,

Zhou,

Liang

et al. 2023

Animals

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The aim of this study was to investigate the molecular mechanisms by which hypoxia affects the biological behavior of yak PASMCs, the changes in the histological structure of yak and cattle lungs, and the relationships and regulatory roles that exist regarding the differences in the distribution and expression of PDK1 and its hypoxia−associated factors screened for their role in the adaptation of yak lungs to the plateau hypoxic environment. The results showed that, at the level of transcriptome sequencing, the molecular regulatory mechanisms of the HIF−1 signaling pathway, glucose metabolism pathway, and related factors (HK2/PGK1/ENO1/ENO3/ALDOC/ALDOA) may be closely related to the adaptation of yaks to the hypoxic environment of the plateau; at the tissue level, the presence of filled alveoli and semi−filled alveoli, thicker alveolar septa and basement membranes, a large number of erythrocytes, capillary distribution, and collagen fibers accounted for all levels of fine bronchioles in the lungs of yaks as compared to cattle. A higher percentage of goblet cells was found in the fine bronchioles of yaks, and PDK1, HIF−1α, and VEGF were predominantly distributed and expressed in the monolayers of ciliated columnar epithelium in the branches of the terminal fine bronchioles of yak and cattle lungs, with a small amount of it distributed in the alveolar septa; at the molecular level, the differences in PDK1 mRNA relative expression in the lungs of adult yaks and cattle were not significant (p > 0.05), the differences in HIF−1α and VEGF mRNA relative expression were significant (p < 0.05), and the expression of PDK1 and HIF−1α proteins in adult yaks was stronger than that in adult cattle. PDK1 and HIF−1α proteins were more strongly expressed in adult yaks than in adult cattle, and the difference was highly significant (p < 0.01); the relative expression of VEGF proteins was not significantly different between adult yaks and cattle (p > 0.05). The possible regulatory relationship between the above results and the adaptation of yak lungs to the plateau hypoxic environment paves the way for the regulatory mechanisms of PDK1, HIF−1α, and VEGF, and provides basic information for studying the mechanism of hypoxic adaptation of yaks in the plateau. At the same time, it provides a reference for human hypoxia adaptation and a target for the prevention and treatment of plateau diseases in humans and plateau animals.

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Physiology and Transcriptomics Analysis Reveal the Contribution of Lungs on High-Altitude Hypoxia Adaptation in Tibetan Sheep

Cited by 4 publications

References 63 publications

Identifying Candidate Genes for Litter Size and Three Morphological Traits in Youzhou Dark Goats Based on Genome-Wide SNP Markers

Identifying Candidate Genes for Litter Size and Three Morphological Traits in Youzhou Dark Goats Based on Genome-Wide SNP Markers

Loss of microRNA-30a and sex-specific effects on the neonatal hyperoxic lung injury

Study of Transcriptomic Analysis of Yak (Bos grunniens) and Cattle (Bos taurus) Pulmonary Artery Smooth Muscle Cells under Oxygen Concentration Gradients and Differences in Their Lung Histology and Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors

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