Ileal transcriptional signatures associated with post-weaning growth in piglets: an exploratory comparison with hypothalamic profiles

Introduction Weaning is a major source of stress and economic lossin pig production, yet the molecular basis of individual variation inpost-weaning average daily gain (ADG) remains poorly understood. Methods We re-analyzed a public RNA-seq dataset (GSE324226)comprising ileal and hypothalamic transcriptomes from 24 pigletsclassified as high or low ADG and slaughtered at day 7 (D7) or day 39(D39) post-weaning ( n = 6 per group and time point). Group, time andtheir interaction were modeled within each tissue, with sex, inferredfrom Y-linked gene expression and unevenly distributed between ADGgroups, included as a covariate Results Few genes were individually differentially expressed. In theileum, genes involved in ribosome biogenesis (NES = 2.73, padj <0.001), rRNA processing and translation, together with independentlycurated MYC target gene sets, were coordinately shifted towardhigher expression in high-ADG piglets. The ribosome-biogenesissignal was strongest at D39, whereas Reactome translation andHallmark MYC-target gene sets were already enriched at D7. Thisrank-based signal was robust to leave-one-animal-out resamplingand to alternative gene-set definitions, but reflected small per-geneeffects (median log 2 FC = 0.26; no leading-edge gene individuallysignificant), did not separate individual animals and was not detectedby single-sample GSVA scores, indicating a group-level transcriptionalsignature; it persisted after adjustment for estimated cell-typecomposition. Ileal cholesterol biosynthesis, tricarboxylic acid cycle andoxidative phosphorylation genes showed a group × time interaction,being higher in high-ADG piglets at D7 and converging by D39.Inferred MYC and ATF6 activities, hypothalamic endoplasmic reticulumstress signatures and cross-tissue ligand–receptor expressioncorrelations did not differ significantly between groups. Discussion In independent datasets, MYC-target and translation genesets were also higher in normal- than in low-birth-weight piglets,whereas acute fasting reduced energy-metabolism but not ribosome-biogenesis gene expression. These exploratory findings nominate ilealribosome-biogenesis gene expression as a candidate transcriptionalcorrelate of post-weaning growth that requires validation at theprotein and functional level.