Gene network analysis identifies rumen epithelial cell proliferation, differentiation and metabolic pathways perturbed by diet and correlated with methane production

Abstract

Ruminants obtain nutrients from microbial fermentation of plant material, primarily in their rumen, a multilayered forestomach. How the different layers of the rumen wall respond to diet and influence microbial fermentation, and how these process are regulated, is not well understood. Gene expression correlation networks were constructed from full thickness rumen wall transcriptomes of 24 sheep fed two different amounts and qualities of a forage and measured for methane production. The network contained two major negatively correlated gene sub-networks predominantly representing the epithelial and muscle layers of the rumen wall. Within the epithelium sub-network gene clusters representing lipid/oxo-acid metabolism, general metabolism and proliferating and differentiating cells were identified. The expression of cell cycle and metabolic genes was positively correlated with dry matter intake, ruminal short chain fatty acid concentrations and methane production. A weak correlation between lipid/oxo-acid metabolism genes and methane yield was observed. Feed consumption level explained the majority of gene expression variation, particularly for the cell cycle genes. Many known stratified epithelium transcription factors had significantly enriched targets in the epithelial gene clusters. The expression patterns of the transcription factors and their targets in proliferating and differentiating skin is mirrored in the rumen, suggesting conservation of regulatory systems.

A high resolution atlas of gene expression in the domestic sheep (Ovis aries)

“…By using comparative clustering information in the pig and the “guilt by association” principle we were able to assign with confidence gene names and putative function to the majority of unannotated genes in clusters 8 (cell-cycle) and 15 (oxidative phosphorylation) (S13 Table). Expression of cell cycle and metabolic genes has recently been shown to be positively correlated with dry matter intake, ruminal short chain fatty acid concentrations and methane production in sheep [52]. In the same study a weak correlation between lipid/oxo-acid metabolism genes and methane yield was also identified suggesting that the newly unannotated genes in these clusters are likely to be relevant in addressing methane production in ruminants [52].…”

“…Expression of cell cycle and metabolic genes has recently been shown to be positively correlated with dry matter intake, ruminal short chain fatty acid concentrations and methane production in sheep [52]. In the same study a weak correlation between lipid/oxo-acid metabolism genes and methane yield was also identified suggesting that the newly unannotated genes in these clusters are likely to be relevant in addressing methane production in ruminants [52].…”

A high resolution atlas of gene expression in the domestic sheep (Ovis aries)

“…By using comparative clustering information in the pig and the “guilt by association” principle we were able to assign with confidence gene names and putative function to the majority of unannotated genes in clusters 8 (cell-cycle) and 15 (oxidative phosphorylation) ( S13 Table ). Expression of cell cycle and metabolic genes has recently been shown to be positively correlated with dry matter intake, ruminal short chain fatty acid concentrations and methane production in sheep [ 52 ]. In the same study a weak correlation between lipid/oxo-acid metabolism genes and methane yield was also identified suggesting that the unannotated genes in these clusters are likely to be relevant in addressing methane production in ruminants [ 52 ].…”

“…Expression of cell cycle and metabolic genes has recently been shown to be positively correlated with dry matter intake, ruminal short chain fatty acid concentrations and methane production in sheep [ 52 ]. In the same study a weak correlation between lipid/oxo-acid metabolism genes and methane yield was also identified suggesting that the unannotated genes in these clusters are likely to be relevant in addressing methane production in ruminants [ 52 ].…”

Across-Experiment Transcriptomics of Sheep Rumen Identifies Expression of Lipid/Oxo-Acid Metabolism and Muscle Cell Junction Genes Associated With Variation in Methane-Related Phenotypes

“…Our previous study ( Xiang et al, 2016a ) identified some of the mechanisms by which the rumen wall interacts with diet which eventually leads to CH 4 production. Unfortunately, gene expression correlation, and gene expression with phenotype correlation, studies are inherently noisy, especially when small numbers of animals are involved.…”