Li Xinpeng, Dong Xinxing, Zhao Shuhong, Ma Yunlong, Jin Siqi, Zhou Chunlu, Lan Yi, Luo Shuyuan, Ni Bin, Wei Hongjiang, Yan Dawei
Faculty of Animal Science and Technology, Yunnan Agricultural University, Yunnan, China.
College of Animal Science and Technology, College of Animal Medicine, Huazhong Agricultural University, Hubei, China.
BMC Biol. 2025 Jul 1;23(1):181. doi: 10.1186/s12915-025-02281-0.
Tibetan pigs, which have long inhabited the Qinghai-Tibet Plateau at elevations exceeding 3000 m, serve as an ideal model for studying adaptation to extreme high-altitude environments. The multifunctionality of the liver (hematopoiesis, metabolism, detoxification) plays a crucial role in the adaptation of Tibetan pigs to hypoxic and cold environments, yet the specific mechanisms remain unclear.
This study employed single-nucleus RNA sequencing to profile and conduct bioinformatic analyses on the liver tissues of Diqing Tibetan pigs across 5 developmental stages (embryonic day 25, embryonic day 55, day of birth, development to 30 days, and development to 90 days). The goal was to identify and investigate key cell types and the regulatory mechanisms of core gene expression that facilitate adaptation to hypoxia and cold. In the fetal liver, various subpopulations of erythrocytes were detected. Analysis of these subpopulations allowed for the construction of a cellular development trajectory from proliferative erythrocytes to division erythrocytes to denucleating erythrocytes, revealing that key transcription factors (JUNB and MAFF) and functional genes (HBP1 and PPP2CB) play significant roles in erythrocyte enucleation. Furthermore, the presence of hematopoietic stem cells in the postnatal liver was observed, with identification of subpopulations exhibiting myeloid differentiation tendencies. These cells continuously support hematopoiesis and facilitate new blood vessel formation, thereby increasing red blood cell counts to aid in the adaptation of Diqing Tibetan pigs to hypoxic conditions. Additionally, a class of hepatocytes capable of converting metabolic energy into heat through uncoupling processes was identified, which assists in the adaptation to the cold environments of the plateau.
In summary, our study provides new scientific perspectives on the adaptation mechanisms of high-altitude animals to extreme environments.
长期栖息于海拔超过3000米的青藏高原的藏猪，是研究适应极端高海拔环境的理想模型。肝脏的多功能性（造血、代谢、解毒）在藏猪适应缺氧和寒冷环境中起着关键作用，但其具体机制仍不清楚。
本研究采用单核RNA测序对迪庆藏猪5个发育阶段（胚胎第25天、胚胎第55天、出生日、发育至30天、发育至90天）的肝脏组织进行分析并开展生物信息学分析。目的是识别和研究促进适应缺氧和寒冷的关键细胞类型及核心基因表达的调控机制。在胎儿肝脏中，检测到了各种红细胞亚群。对这些亚群的分析使得构建从增殖红细胞到分裂红细胞再到去核红细胞的细胞发育轨迹成为可能，揭示了关键转录因子（JUNB和MAFF）和功能基因（HBP1和PPP2CB）在红细胞去核过程中发挥着重要作用。此外，在出生后的肝脏中观察到了造血干细胞的存在，并鉴定出了表现出髓系分化倾向的亚群。这些细胞持续支持造血并促进新血管形成，从而增加红细胞数量，以帮助迪庆藏猪适应缺氧环境。此外，还鉴定出了一类能够通过解偶联过程将代谢能量转化为热量的肝细胞，这有助于适应高原的寒冷环境。
总之，我们的研究为高海拔动物适应极端环境的机制提供了新的科学视角。
Zotero 插件
