Transcriptomic Profiling of Hypoxia-Adaptive Responses in Tibetan Goat Fibroblasts
The Tibetan goat (<i>Capra hircus</i>) exhibits remarkable adaptations to high-altitude hypoxia, yet the molecular mechanisms remain unclear. This study integrates RNA-seq, WGCNA, and machine learning to explore gene-environment interactions (G × E) in hypoxia adaptation. Fibroblasts fro...
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MDPI AG
2025-05-01
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| author | Lin Tang Li Zhu Zhuzha Basang Yunong Zhao Shanshan Li Xiaoyan Kong Xiao Gou |
| author_facet | Lin Tang Li Zhu Zhuzha Basang Yunong Zhao Shanshan Li Xiaoyan Kong Xiao Gou |
| author_sort | Lin Tang |
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| description | The Tibetan goat (<i>Capra hircus</i>) exhibits remarkable adaptations to high-altitude hypoxia, yet the molecular mechanisms remain unclear. This study integrates RNA-seq, WGCNA, and machine learning to explore gene-environment interactions (G × E) in hypoxia adaptation. Fibroblasts from the Tibetan goat and Yunling goat were cultured under hypoxic (1% O<sub>2</sub>) and normoxic (21% O<sub>2</sub>) conditions, respectively. This identified 68 breed-specific (G), 100 oxygen-responsive (E), and 620 interaction-driven (I) Differentially Expressed Genes (DEGs). The notably higher number of interaction-driven DEGs compared to other effects highlights transcriptional plasticity. We defined two gene sets: Environmental Stress Genes (<i>n</i> = 632, E ∪ I) and Genetic Adaptation Genes (<i>n</i> = 659, G ∪ I). The former were significantly enriched in pathways related to oxidative stress defense and metabolic adaptation, while the latter showed prominent enrichment in pathways associated with vascular remodeling and transcriptional regulation. <i>CTNNB1</i> emerged as a key regulatory factor in both gene sets, interacting with <i>CASP3</i> and <i>MMP2</i> to form the core of the protein–protein interaction (PPI) network. Machine learning identified <i>MAP3K5</i>, <i>TGFBR2</i>, <i>RSPO1</i> and <i>ITGB5</i> as critical genes. WGCNA identified key modules in hypoxia adaptation, where <i>FOXO3</i>, <i>HEXIM1</i>, and <i>PPARD</i> promote the stabilization of <i>HIF-1α</i> and metabolic adaptation through the HIF-1 signaling pathway and glycolysis. These findings underscore the pivotal role of gene–environment interactions in hypoxic adaptation, offering novel perspectives for both livestock breeding programs and biomedical research initiatives. |
| format | Article |
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| institution | OA Journals |
| issn | 2076-2615 |
| language | English |
| publishDate | 2025-05-01 |
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| series | Animals |
| spelling | doaj-art-4850d1ff8db74fac8a18dcdf8ef1908c2025-08-20T01:56:56ZengMDPI AGAnimals2076-26152025-05-011510140710.3390/ani15101407Transcriptomic Profiling of Hypoxia-Adaptive Responses in Tibetan Goat FibroblastsLin Tang0Li Zhu1Zhuzha Basang2Yunong Zhao3Shanshan Li4Xiaoyan Kong5Xiao Gou6Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, ChinaFaculty of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, ChinaInstitute of Animal Husbandry and Veterinary Science, Xizang Autonomous Region Academy of Agricultural and Animal Husbandry Sciences, Lhasa 850009, ChinaSchool of Animal Science and Technology, Foshan University, Foshan 528231, ChinaSchool of Animal Science and Technology, Foshan University, Foshan 528231, ChinaFaculty of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, ChinaSchool of Animal Science and Technology, Foshan University, Foshan 528231, ChinaThe Tibetan goat (<i>Capra hircus</i>) exhibits remarkable adaptations to high-altitude hypoxia, yet the molecular mechanisms remain unclear. This study integrates RNA-seq, WGCNA, and machine learning to explore gene-environment interactions (G × E) in hypoxia adaptation. Fibroblasts from the Tibetan goat and Yunling goat were cultured under hypoxic (1% O<sub>2</sub>) and normoxic (21% O<sub>2</sub>) conditions, respectively. This identified 68 breed-specific (G), 100 oxygen-responsive (E), and 620 interaction-driven (I) Differentially Expressed Genes (DEGs). The notably higher number of interaction-driven DEGs compared to other effects highlights transcriptional plasticity. We defined two gene sets: Environmental Stress Genes (<i>n</i> = 632, E ∪ I) and Genetic Adaptation Genes (<i>n</i> = 659, G ∪ I). The former were significantly enriched in pathways related to oxidative stress defense and metabolic adaptation, while the latter showed prominent enrichment in pathways associated with vascular remodeling and transcriptional regulation. <i>CTNNB1</i> emerged as a key regulatory factor in both gene sets, interacting with <i>CASP3</i> and <i>MMP2</i> to form the core of the protein–protein interaction (PPI) network. Machine learning identified <i>MAP3K5</i>, <i>TGFBR2</i>, <i>RSPO1</i> and <i>ITGB5</i> as critical genes. WGCNA identified key modules in hypoxia adaptation, where <i>FOXO3</i>, <i>HEXIM1</i>, and <i>PPARD</i> promote the stabilization of <i>HIF-1α</i> and metabolic adaptation through the HIF-1 signaling pathway and glycolysis. These findings underscore the pivotal role of gene–environment interactions in hypoxic adaptation, offering novel perspectives for both livestock breeding programs and biomedical research initiatives.https://www.mdpi.com/2076-2615/15/10/1407gene–environment interactionsDEGsmachine learningWGCNAHIF-1 signaling pathway |
| spellingShingle | Lin Tang Li Zhu Zhuzha Basang Yunong Zhao Shanshan Li Xiaoyan Kong Xiao Gou Transcriptomic Profiling of Hypoxia-Adaptive Responses in Tibetan Goat Fibroblasts Animals gene–environment interactions DEGs machine learning WGCNA HIF-1 signaling pathway |
| title | Transcriptomic Profiling of Hypoxia-Adaptive Responses in Tibetan Goat Fibroblasts |
| title_full | Transcriptomic Profiling of Hypoxia-Adaptive Responses in Tibetan Goat Fibroblasts |
| title_fullStr | Transcriptomic Profiling of Hypoxia-Adaptive Responses in Tibetan Goat Fibroblasts |
| title_full_unstemmed | Transcriptomic Profiling of Hypoxia-Adaptive Responses in Tibetan Goat Fibroblasts |
| title_short | Transcriptomic Profiling of Hypoxia-Adaptive Responses in Tibetan Goat Fibroblasts |
| title_sort | transcriptomic profiling of hypoxia adaptive responses in tibetan goat fibroblasts |
| topic | gene–environment interactions DEGs machine learning WGCNA HIF-1 signaling pathway |
| url | https://www.mdpi.com/2076-2615/15/10/1407 |
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