单核RNA测序确定了有助于藏猪适应寒冷的脂肪组织亚群。

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

作者信息

Liu Jiali, Jiang Yao, Liu Tianxia, Chen Chuanhe, Chui Linya, Cui Along, Zhang Xueping, Wang Xiao, Wang Yu, Yang Chunhuai, Zhang Ying, Wu Tianwen, Yang Shulin, Huang Jiaojiao, Tao Cong, Zhao Jianguo, Wang Yanfang

机构信息

State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China.

National Animal Husbandry Service, Beijing, 100125, China.

出版信息

BMC Biol. 2025 Apr 24;23(1):107. doi: 10.1186/s12915-025-02211-0.

DOI:10.1186/s12915-025-02211-0

PMID:40275312

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12023645/

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, PDGFRαEBF2 in IAT and ADIPOQHIF1A in both depots. PDGFRαEBF2 cells were characterized as potential beige precursors, while ADIPOQHIF1A 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 PDGFRαEBF2 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.

摘要

背景

产热米色脂肪细胞在哺乳动物中具有显著的适应寒冷环境的能力，但其潜在的细胞机制仍不清楚，尤其是在缺乏功能性解偶联蛋白1（UCP1）的猪中。

结果

短期冷暴露（4℃，3天）后，在藏猪（耐寒）和巴马猪（冷敏感）中均观察到多泡米色脂肪细胞。通过对两种猪在室温及冷处理条件下的皮下腹股沟脂肪组织（IAT）和肾周脂肪组织（PAT）等脂肪组织进行单核RNA测序，我们发现了藏猪特有的两个细胞亚群，IAT中的PDGFRαEBF2和两个脂肪库中的ADIPOQHIF1A。PDGFRαEBF2细胞被表征为潜在的米色前体细胞，而ADIPOQHIF1A细胞被发现高度表达与产热相关的基因。尽管在冷处理后两种猪中均观察到生脂亚群减少，脂解和产热亚群增加，但藏猪与巴马猪相比表现出更强的细胞和分子反应。值得注意的是，冷诱导的新生米色脂肪生成和白色脂肪细胞褐变可能发生在藏猪中，而巴马猪更依赖白色脂肪褐变。此外，在PDGFRαEBF2亚群中高表达的骨形态发生蛋白7（BMP7）正向调节猪的米色产热能力。