The transcriptomic and regulatory dynamics of the rumen epithelium of sheep

The rumen is the interface between the diet, rumen microbes and the animal. However a fundamental mechanistic understanding of the control of the rumen epithelial interactions is lacking. We performed comparative transcriptomic analysis of the whole rumen wall of sheep measured for methane production and other rumen-based traits in two different datasets, including one with four combinations of amount and composition of diet. Few genes from the muscle layer were significantly responsive to diet. In contrast genes involved in cell cycle (proliferation of epithelial cells) and rumen metabolism (also in the epithelial layer) were the most dynamic signals and responded to different diets. The majority of gene expression and phenotypic variation was explained by feed consumption level. Using a network approach metabolic genes were further separable based on general cellular (electron transport and intracellular transport) and rumen-specific (keto-acids and lipids) processes. Enrichment of transcription factor binding sites in genes with correlated expression identified potential key transcription factors actively expressed in the rumen epithelial layer with roles in regulating epidermal cell division and differentiation. Many of the transcription factors identified have characterised roles in skin growth and similar expression patterns in human skin and sheep rumen relative to other genes. It appears likely that the control of rumen growth is a combination of generic epithelial processes (such as in the skin) and rumen specific processes. Our results demonstrate the promise of transcriptomics to elucidate the mechanisms of regulation of rumen epithelial growth and interaction with diet and the microbial populations.