Transcriptomic profiling of intestinal mesenchymal stromal cells reveals age-dependent gene expression changes during postnatal development in pre-weaned piglets

Recent studies showed that intestinal mesenchymal stromal cells (iMSCs) regulate the functional maturation of gastrointestinal tissues during postnatal development in mice. Despite their significant findings, the roles of iMSCs during postnatal development in piglets remain unknown. Considering the gut physiologic and developmental similarities in piglets and human neonates and their translational advantage over mice as animal models, we aim to explore RNA sequencing of days 0, 7, and 21 jejunal iMSCs from piglets to study the transcriptomic changes during postnatal development. We hypothesize that, like human and mouse postnatal iMSCs, piglets’ iMSCs may exhibit dynamic transcriptomic profiles across different stages of postnatal intestinal development in preweaned piglets. The sequencing data of the piglets’ jejunal iMSC shows significant variation in gene expressions among the time points (q-value ≤ 0.05). We observe that most genes enhanced in day 0 iMSCs are related to cell proliferation, whereas those enhanced in day 21 iMSCs are associated with diverse functional regulations. For instance, top upregulated genes in day 21 iMSCs support varied cellular and molecular processes, including structural support ( COL5A3, LUM ), tissue remodeling ( VCAM1 ), terminal differentiation ( FGF2, PDGFRA, CD55, SMOC1 ), nutrient absorption ( SLC2A5, SLC2A3, SLC43A2 ), and microbial and immune responses ( IL6, CXCL8, IL11, TNFA1P3, IL13RA1, SIRPA ). Real-time PCR analysis of key iMSC secretomes that are associated with epithelial development further reveals differential gene expression patterns among the age groups, with BMP4 upregulated on day 7, whereas GREM1 and SFRP1 mostly enhanced on day 21 (P-value ≤ 0.05). Consistently, our histological study showed that the day 7 iMSCs showed significantly longer villi compared to other ages. Additionally, our functional study using a co-culture model of enteroids and the different iMSC age groups showed an age-specific functional influence of iMSCs on intestinal organoid growth. Together, the current study highlights a dynamic transcriptomic switch in postnatal jejunal iMSCs and may play key modulatory roles during postnatal intestinal development in the piglet intestine. This information lays essential groundwork for upcoming functional studies of porcine iMSCs, highlighting its potential as a translational model for human neonates. The authors appreciate financial support from the MAES Competitive Grant Program at the University of Maryland, College Park, USA. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.