2. Academic Validation
  3. Single-nucleus RNA sequencing defines adipose tissue subpopulations that contribute to Tibetan pig cold adaptation

Single-nucleus RNA sequencing defines adipose tissue subpopulations that contribute to Tibetan pig cold adaptation

  • BMC Biol. 2025 Apr 24;23(1):107. doi: 10.1186/s12915-025-02211-0.
Jiali Liu 1,  Yao Jiang 2,  Tianxia Liu 3 4 5,  Chuanhe Chen 1,  Linya Chui 1 6,  Along Cui 3 5 7,  Xueping Zhang 1 3 8,  Xiao Wang 1,  Yu Wang 3 4 5,  Chunhuai Yang 1,  Ying Zhang 3 5 9,  Tianwen Wu 1,  Shulin Yang 1,  Jiaojiao Huang 6,  Cong Tao 10,  Jianguo Zhao 11 12 13 14 15,  Yanfang Wang 16 17
Affiliations

Affiliations

  • 1 State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China.
  • 2 National Animal Husbandry Service, Beijing, 100125, China.
  • 3 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 4 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 5 Lnstitute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
  • 6 College of Life Sciences, Qingdao Agricultural University, Qingdao, 266109, China.
  • 7 Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
  • 8 College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China.
  • 9 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
  • 10 State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. taocong@caas.cn.
  • 11 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. zhaojg@ioz.ac.cn.
  • 12 University of Chinese Academy of Sciences, Beijing, 100049, China. zhaojg@ioz.ac.cn.
  • 13 Lnstitute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. zhaojg@ioz.ac.cn.
  • 14 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China. zhaojg@ioz.ac.cn.
  • 15 Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya, 572025, China. zhaojg@ioz.ac.cn.
  • 16 State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. wangyanfang@caas.cn.
  • 17 Sanya Institute, Hainan Academy of Agricultural Sciences, Sanya, 572025, China. wangyanfang@caas.cn.
PMID: 40275312 DOI: 10.1186/s12915-025-02211-0
Abstract

Background: Thermogenic beige adipocyte displays a remarkable ability in mammals to adapt to cold environments, but the underlying cellular mechanisms remain unclear, especially in pigs that lack functional UCP1.

Results: Multilocular beige adipocytes were observed in both Tibetan pigs (cold-tolerant) and Bama pigs (cold-sensitive) after short-term cold exposure (4 ℃ for 3 days). Through single-nucleus RNA Sequencing of adipose tissues, including subcutaneous inguinal adipose tissues (IAT) and perirenal adipose tissues (PAT), from both pig breeds at room temperature and cold treatment conditions, we discovered two cell subpopulations specific to Tibetan pigs, PDGFRα+EBF2High in IAT and ADIPOQ+HIF1AHigh in both depots. PDGFRα+EBF2High cells were characterized as potential beige precursors, while ADIPOQ+HIF1AHigh cells were found to express highly thermogenic-related genes. Despite the decrease of the lipogenic subpopulation and the increase of the lipolytic and the thermogenic subpopulations observed in both pig breeds upon cold treatment, Tibetan pigs exhibited stronger cellular and molecular responses compared to Bama pigs. Remarkably, cold-induced de novo beige adipogenesis and white adipocyte browning, likely occurred in Tibetan pigs, while Bama pigs relied more heavily on white browning. Moreover, BMP7, which was highly expressed in the PDGFRα+EBF2High subpopulation, positively regulates porcine beige thermogenic capacity.

Conclusions: Our data offers a comprehensive and unprecedented perspective on the heterogeneity and plasticity of adipose tissues of pigs and broadens the understanding of beige fat biology in mammals.

Keywords

Adipocytes; Cold stimulation; Pig; Subpopulations; snRNA-seq.

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