Adaptation of Diqing Tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liver

Abstract Background 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...

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Main Authors: Xinpeng Li, Xinxing Dong, Shuhong Zhao, Yunlong Ma, Siqi Jin, Chunlu Zhou, Yi Lan, Shuyuan Luo, Bin Ni, Hongjiang Wei, Dawei Yan
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Biology
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Online Access:https://doi.org/10.1186/s12915-025-02281-0
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author Xinpeng Li
Xinxing Dong
Shuhong Zhao
Yunlong Ma
Siqi Jin
Chunlu Zhou
Yi Lan
Shuyuan Luo
Bin Ni
Hongjiang Wei
Dawei Yan
author_facet Xinpeng Li
Xinxing Dong
Shuhong Zhao
Yunlong Ma
Siqi Jin
Chunlu Zhou
Yi Lan
Shuyuan Luo
Bin Ni
Hongjiang Wei
Dawei Yan
author_sort Xinpeng Li
collection DOAJ
description Abstract Background 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. Results 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. Conclusions In summary, our study provides new scientific perspectives on the adaptation mechanisms of high-altitude animals to extreme environments.
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language English
publishDate 2025-07-01
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spelling doaj-art-022108a0d18b4132a1f491a43f1a42b32025-08-20T03:45:36ZengBMCBMC Biology1741-70072025-07-0123112810.1186/s12915-025-02281-0Adaptation of Diqing Tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liverXinpeng Li0Xinxing Dong1Shuhong Zhao2Yunlong Ma3Siqi Jin4Chunlu Zhou5Yi Lan6Shuyuan Luo7Bin Ni8Hongjiang Wei9Dawei Yan10Faculty of Animal Science and Technology, Yunnan Agricultural UniversityFaculty of Animal Science and Technology, Yunnan Agricultural UniversityCollege of Animal Science and Technology, College of Animal Medicine, Huazhong Agricultural UniversityCollege of Animal Science and Technology, College of Animal Medicine, Huazhong Agricultural UniversityFaculty of Animal Science and Technology, Yunnan Agricultural UniversityFaculty of Animal Science and Technology, Yunnan Agricultural UniversityFaculty of Animal Science and Technology, Yunnan Agricultural UniversityFaculty of Animal Science and Technology, Yunnan Agricultural UniversityFaculty of Animal Science and Technology, Yunnan Agricultural UniversityFaculty of Animal Science and Technology, Yunnan Agricultural UniversityFaculty of Animal Science and Technology, Yunnan Agricultural UniversityAbstract Background 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. Results 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. Conclusions In summary, our study provides new scientific perspectives on the adaptation mechanisms of high-altitude animals to extreme environments.https://doi.org/10.1186/s12915-025-02281-0Diqing Tibetan pigSingle-nucleus transcriptome sequencingHematopoietic stem cellsHepatocytesHypoxia and cryogenic adaptation
spellingShingle Xinpeng Li
Xinxing Dong
Shuhong Zhao
Yunlong Ma
Siqi Jin
Chunlu Zhou
Yi Lan
Shuyuan Luo
Bin Ni
Hongjiang Wei
Dawei Yan
Adaptation of Diqing Tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liver
BMC Biology
Diqing Tibetan pig
Single-nucleus transcriptome sequencing
Hematopoietic stem cells
Hepatocytes
Hypoxia and cryogenic adaptation
title Adaptation of Diqing Tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liver
title_full Adaptation of Diqing Tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liver
title_fullStr Adaptation of Diqing Tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liver
title_full_unstemmed Adaptation of Diqing Tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liver
title_short Adaptation of Diqing Tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liver
title_sort adaptation of diqing tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liver
topic Diqing Tibetan pig
Single-nucleus transcriptome sequencing
Hematopoietic stem cells
Hepatocytes
Hypoxia and cryogenic adaptation
url https://doi.org/10.1186/s12915-025-02281-0
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