|GAO, YAHUI - Shandong Academy Of Agricultural Sciences|
|LI, JIAN-BIN - Shandong Academy Of Agricultural Sciences|
|CAI, GAOZHAN - Shandong Academy Of Agricultural Sciences|
|WANG, YUJIAO - Shandong Academy Of Agricultural Sciences|
|YANG, WENJING - Shandong Academy Of Agricultural Sciences|
|LI, YANQIN - Shandong Academy Of Agricultural Sciences|
|ZHAO, XIUXIN - Shandong Academy Of Agricultural Sciences|
|LI, RONGLING - Collaborator|
|GAO, YUNDONG - Collaborator|
|Baldwin, Ransom - Randy|
|Li, Congjun - Cj|
|FANG, LINGZHAO - University Of Edinburgh|
|Liu, Ge - George|
Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/13/2022
Publication Date: 4/30/2022
Citation: Gao, Y., Li, J., Cai, G., Wang, Y., Yang, W., Li, Y., Zhao, X., Li, R., Gao, Y., Tuo, W., Baldwin, R.L., Li, C., Fang, L., Liu, G.E. 2022. Single-cell transcriptomic and chromatin accessibility analyses of dairy cattle peripheral blood mononuclear cells and their responses to lipopolysaccharide. BMC Genomics. 23:338. https://doi.org/10.1186/s12864-022-08562-0.
Interpretive Summary: Comprehensive analyses of tissues at single-cell level will benefit our understanding of genetic bases for complex traits. We provided the first cell type profiles for cattle peripheral blood mononuclear cells and examined their responses to lipopolysaccharide. These results fill our knowledge gaps and provide the foundation for incorporating new transcriptome insights into the future animal breeding program. Farmers, scientist, and policy planners who need improve animal health and production based on genome-enabled animal selection will benefit from this study.
Technical Abstract: Using cell-specific marker genes, we obtained seven distinct cell clusters/cell types from 26,141 single cell RNA sequencing data of four cattle peripheral blood mononuclear cell (PBMC) samples before and during lipopolysaccharide (LPS) treatment. We annotated these immune cell types and examined their responses to LPS by performing cell cycle, pseudotime trajectory, regulatory network, gene co-expression network, gene ontology, differentially expressed genes (DEGs) chromatin accessibility analyses. Our results revealed LPS could induce host B cell proliferation and activation of monocytes, dendritic cells, and macrophages through TLR4 receptor binding, which activates transcription factors like NF-kB and promotes the secretion of pro-inflammatory cytokines and other molecules to launch innate and adaptive immune responses. By integrating these DEGs with Holstein GWAS signals, we found they were enriched for animal production and body conformation traits. Finally, we confirmed their cell identities by comparing them with a human PBMC sample. This study presents the first effort to implement single-cell transcriptomic analysis in cattle PBMC, and demonstrates immune blood cell types and their responses during LPS treatment, opening the door for discoveries about tissue/cell type roles in complex traits at single-cell resolution.