scRNA-Seq reveals the potential roles of transposable elements in bovine mastitis

Bovine mastitis is one of the most common and important inflammatory diseases that has significant implications in the dairy industry, in terms of both animal welfare and economic aspects. Transposable elements (TEs), a major component of the eukaryotic genome, were once thought to have little or no function/activity, but recent studies have shown the significance of TEs in different diseases, particularly their potential to modulate immune responses. However, the contribution of TEs to mastitis remain largely unknown. Furthermore, cell-type-specific patterns related to TE transcripts have not been reported in bovine mastitis.

Here, single-cell RNA sequencing employed to profile the expression patterns of TEs in 27,729 cells derived from bovine peripheral blood mononuclear cells, cultured in vitro before and after LPS stimulation. Through a systematic single-cell investigation, seven major cell-types were identified that were used to investigate the contribution of TEs to the regulatory mechanisms involved in the immune response of cells to LPS-induced mastitis.

The findings revealed that TEs contribute to cell heterogeneity, emphasizing their potential as biomarkers. We found TE loci that exhibited cell-type specific expression patterns and were also overlapped with genes related to function of that cell-type. Interestingly, we observed a striking pattern, in which the mean expression of TEs across all cell-types were increased in LPS-treated samples than control, especially in T, B and HSC/MPP cell-types, which are the main players of the immune system. This pattern revealed that the activation of TEs may mediate cells to immune response to infection. Moreover, several examples were found in which expression of TEs have been significantly and positively linked to expression of neighboring genes, supporting the extensive contribution of TEs during mastitis. Interestingly, most of the TE-gene pairs whose expression were significantly associated, were those that were reported to be involved in mastitis or immune response such as BOV-A2, Bov-tA2, MIR3, MIRb, L2a, PAX5, IL1RN, GRB2, CCR7, NFKBIE, EPSTI1, ZEB2, IRF8, CD22 and STIM1.

Our study shows the potential of TEs as important mediators of immune system whereby can contribute to coordinated transcriptional responses during infection and act as major drivers of disorders such as mastitis.