Cross one single body 49 tissues single-cell transcriptome reveals detailed macrophage heterogeneity during pig
Xiaoyun Chen1, Chenliang Lai1, Liping Cai1
1National Key Laboratory for Swine Genetic Improvement and Germplasm Innovation, Ministry of Science and Technology of China, Jiangxi Agricultural University, Nanchang, China.
Introduction:
Pregnancy involves complex physiological adaptations across maternal organs and the immune system to support fetal development. Macrophages play a dual role during pregnancy: defending against pathogens and supporting tissue adaptation. However, comprehensive and in-depth studies of cross-tissue transcriptional heterogeneity of macrophages during healthy pregnancy at the single-cell level remain elusive.
Methods:
We performed single-cell RNA sequencing (scRNA-seq) to profile macrophages from a healthy pregnant pig across 49 tissues. Immunofluorescence was performed to verify the specific expression of transcription factors.
Results:
In this study, we generated a macrophage atlas containing 114,881 macrophages from 49 tissues/organs within one single healthy pregnant pig, identified 33 subtypes, and revealed extensive tissue-specific diversity. We observed significant heterogeneity of macrophage subtypes across five different anatomical sites of adipose tissue. Notably, the Mφ MARCO+ subtype, primarily derived from mesenteric adipose tissue, showed higher activity in pattern recognition receptor signaling pathways compared to subtypes in other tissues, including different fat depots. Cross-tissue analysis revealed distinct expression patterns of transcription factors, cytokines, and cell surface receptors, including the transcription factor PLSCR1, specifically expressed in lung macrophages and verified by immunofluorescence. Cross-species analysis unveiled conservation and heterogeneity among macrophages in pigs, humans, and mice.
Conclusion:
We constructed a multiple-tissue single-cell transcriptome atlas of macrophages in one single healthy pregnant pig, revealing their molecular differences and commonalities across tissues and species. Our study provides a valuable resource for understanding macrophage diversity and tissue-specific macrophage adaptations during pregnancy in pigs.
