Fetal-like reversion in the regenerating intestine is regulated by mesenchymal Asporin

Mesenchymal cells and the extracellular matrix (ECM) support epithelium during homeostasis and regeneration. We modeled epithelial regeneration by culturing intestinal epithelium on decellularized small intestinal scaffolds (iECM), and identify Asporin (Aspn), an ECM bound proteoglycan, as a critical mediator of epithelial fetal-like reprogramming. To investigate its role in modulating intestinal epithelial cell states, we performed RNA sequencing (RNAseq) on small intestinal organoids treated with recombinant Aspn. This dataset provides a transcriptional profile of Aspn-treated intestinal epithelial cells, highlighting gene expression changes associated with fetal-like reprogramming and regenerative processes. The analysis offers insights into how Aspn influences epithelial signaling pathways, including TGF-beta signaling, underlying epithelial plasticity and the ECM's role in coordinating tissue responses to injury.