Regeneration signatures of TGFB1-treated mouse intestinal organoids and Ki67 positive primary cells sorted from mice after irradiation

The adult gut epithelium has a remarkable ability to recover from damage, a process that involves a temporary transition to a fetal-like state during regeneration. To achieve the goal of cellular therapies to restore and/or replace defective gastrointestinal epithelia, it is important to discover the natural components of the regenerative process. We employed a combination of –omics approaches, mouse genetic models, and murine and human organoids to characterize a role for TGFB in recovery from irradiation. In organoid culture conditions, TGFB1-treatment was necessary and sufficient to induce a transcriptomic shift to the fetal-like/regenerative state. Bulk RNA-seq, scRNA-seq and ATAC-seq were employed to profile vehicle and TGFB1-treated organoids. scRNA-seq was also employed to profile Ki67-RFP positive cells isolated from Mki67tm1.1Cle/J mice after 56 hours post-irradiation and their non-IR littermate control.