Single-cell transcriptome uncovers heterogeneity and distinct states of ileum between suckling and early-weaning piglets

We set out to better understand the cellular heterogeneity and niche cues of the remodeling porcine intestine after weaning by performing single-cell mRNA sequencing (scRNA-seq) survey of 42,149 cells from ileum tissue in piglets. Substantial heterogeneity among diverse epithelial, stromal, and immune cell subsets was observed. We map the various cell committed state within ileum tissue, and connect them through cell-cell interactions. We delineated a new classification of different epithelium secretory cells. Apart from goblet cell and enteroendocrine cell, we found that few pH-sensing BEST4/OTOP2 cells also exist in the ileum13. The immune component of early-weaned piglet was shifted as reduction of Th17 and abundance of CTL. Th17 cells harbor features of classical phonotype in normal suckling piglet (NSP) and pathogenicity in early weaning piglet (EWP), which may be induced by special cytokine milieu suggested as previous stduy14,15. We conclusively showed enrichment of the pathogenic effector CD8+ GZMB+ CTL cells may be a critical factor exacerbating ileal inflammation via mitochondrial dysfunction inducing epithelia cell apoptosis in EWP. Overall design: Three litters (Landrace x Yorkshire, 12 piglets per litter) were selected. At 21 d of age (pre-weaning stage), piglets of each litter were randomly allotted to two groups (n = 6) as follows: the EWP group was moved in farrowing barn without sow; the NSP group was continuously nursed by sows during full-trial period.