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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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Animals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2615/15/10/1407 |
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| Summary: | 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. |
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| ISSN: | 2076-2615 |