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Single-cell transcriptomic and chromatin accessibility analyses of dairy cattle peripheral blood mononuclear cells and their responses to lipopolysaccharide

文献类型： 外文期刊

作者： Gao, Yahui 1 ; Li, Jianbin 1 ; Cai, Gaozhan 1 ; Wang, Yujiao 1 ; Yang, Wenjing 4 ; Li, Yanqin 1 ; Zhao, Xiuxin 3 ; Li, Rongling 1 ; Gao, Yundong 1 ; Tuo, Wenbin 5 ; Baldwin, Ransom L. 2 ; Li, Cong-Jun 2 ; Fang, Lingzhao 6 ; Liu, George E. 2 ;

作者机构： 1.Shandong Acad Agr Sci, Inst Anim Sci & Vet Med, 202 Gongyebei Rd, Jinan 250100, Peoples R China

2.USDA ARS, Anim Genom & Improvement Lab, BARC, Beltsville, MD 20705 USA

3.Shandong Ox Livestock Breeding Co Ltd, Jinan 250100, Peoples R China

4.China Agr Univ, Coll Anim Sci & Technol, Beijing 100193, Peoples R China

5.USDA ARS, Anim Parasit Dis Lab, BARC, Beltsville, MD 20705 USA

6.Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

关键词： Cattle; Peripheral blood mononuclear cell; Lipopolysaccharide; Single-cell RNA-seq; Single-cell ATAC-seq

期刊名称：BMC GENOMICS （ 影响因子：4.547； 五年影响因子：4.931 ）

ISSN： 1471-2164

年卷期： 2022 年 23 卷 1 期

页码：

收录情况： SCI

摘要： Background Gram-negative bacteria are important pathogens in cattle, causing severe infectious diseases, including mastitis. Lipopolysaccharides (LPS) are components of the outer membrane of Gram-negative bacteria and crucial mediators of chronic inflammation in cattle. LPS modulations of bovine immune responses have been studied before. However, the single-cell transcriptomic and chromatin accessibility analyses of bovine peripheral blood mononuclear cells (PBMCs) and their responses to LPS stimulation were never reported. Results We performed single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) in bovine PBMCs before and after LPS treatment and demonstrated that seven major cell types, which included CD4 T cells, CD8 T cells, and B cells, monocytes, natural killer cells, innate lymphoid cells, and dendritic cells. Bioinformatic analyses indicated that LPS could increase PBMC cell cycle progression, cellular differentiation, and chromatin accessibility. Gene analyses further showed significant changes in differential expression, transcription factor binding site, gene ontology, and regulatory interactions during the PBMC responses to LPS. Consistent with the findings of previous studies, LPS induced activation of monocytes and dendritic cells, likely through their upregulated TLR4 receptor. NF-kappa B was observed to be activated by LPS and an increased transcription of an array of pro-inflammatory cytokines, in agreement that NF-kappa B is an LPS-responsive regulator of innate immune responses. In addition, by integrating LPS-induced differentially expressed genes (DEGs) with large-scale GWAS of 45 complex traits in Holstein, we detected trait-relevant cell types. We found that selected DEGs were significantly associated with immune-relevant health, milk production, and body conformation traits. Conclusion This study provided the first scRNAseq and scATAC-seq data for cattle PBMCs and their responses to the LPS stimulation to the best of our knowledge. These results should also serve as valuable resources for the future study of the bovine immune system and open the door for discoveries about immune cell roles in complex traits like mastitis at single-cell resolution.

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