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Hypoxia-Driven Pulmonary Adaptation in the Yak: A Homeostatic Mechanism Mediated by Cell Adhesion Molecules

Year: 2026

Type: article

Abstract: Cell adhesion molecules (CAMs) are key regulators of tissue structural integrity and functional coordination, yet their specific role in the adaptation of yak lung tissue to high-altitude hypoxia remains unelucidated. Thus, we employed transcriptomic sequencing (RNA-seq), molecular biology assays, and single-cell RNA-seq (scRNA-seq) to analyze the expression characteristics of CAMs in yak lung tissues at high and low altitudes. Trypsin or collagenase digestion showed higher cell counts in high-altitude yak lungs (p < 0.05). RNA-seq analysis revealed significant enrichment of differentially expressed genes (DEGs) in adhesion-related pathways. Inductively coupled plasma mass spectrometry detected elevated Ca2+ levels in high-altitude yak lungs (p < 0.05). Quantitative real-time PCR (qRT-PCR) detection of key genes from five major families of CAMs revealed the downregulation of cadherin and integrin family-related genes, and upregulation of immunoglobulin superfamily-related genes, in high-altitude yak lungs (p < 0.05), corroborated by immunohistochemical (IHC) staining. A 10× scRNA-seq revealed adhesion changes in 9 of 15 lung cell subpopulations, with differentially expressed CAMs involving integrins. This study demonstrates that yak lung tissue establishes a sophisticated adhesive homeostasis through differential CAMs regulation. This strategy optimizes pulmonary immune responses and energy allocation, ensures structural integrity and functional coordination, and thereby facilitates superior acclimatization to higher-altitude hypoxia.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27031368