{"doi":"10.1101/2023.01.13.523825","title":"TGFB1 Induces Fetal Reprogramming and Enhances Intestinal Regeneration","abstract":"The adult gut epithelium has a remarkable ability to recover from damage. To achieve cellular therapies aimed at restoring and/or replacing defective gastrointestinal tissue, it is important to understand the natural mechanisms of tissue regeneration. We employed a combination of high throughput sequencing approaches, mouse genetic models, and murine and human organoid models, and identified a role for TGFB signaling during intestinal regeneration following injury. At 2 days following irradiation (IR)-induced damage of intestinal crypts, a surge in TGFB1 expression is mediated by monocyte/macrophage cells at the location of damage. Depletion of macrophages or genetic disruption of TGFB-signaling significantly impaired the regenerative response following irradiation. Murine intestinal regeneration is also characterized by a process where a fetal transcriptional signature is induced during repair. In organoid culture, TGFB1-treatment was necessary and sufficient to induce a transcriptomic shift to the fetal-like/regenerative state. The regenerative response was enhanced by the function of mesenchymal cells, which are also primed for regeneration by TGFB1. Mechanistically, integration of ATAC-seq, scRNA-seq, and ChIP-seq suggest that a regenerative YAP-SOX9 transcriptional circuit is activated in epithelium exposed to TGFB1. Finally, pre-treatment with TGFB1 enhanced the ability of primary epithelial cultures to engraft into damaged murine colon, suggesting promise for the application of the TGFB-induced regenerative circuit in cellular therapy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390476,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":679451,"name":"Abigail Dupre","orcid":null,"position":1,"is_corresponding":false},{"id":49067,"name":"Xia Qiu","orcid":"0000-0002-3694-7357","position":2,"is_corresponding":false},{"id":371184,"name":"Oscar Pellón-Cárdenas","orcid":"0000-0003-3085-1618","position":3,"is_corresponding":false},{"id":318755,"name":"Katherine D. Walton","orcid":"0000-0001-9108-5617","position":4,"is_corresponding":false},{"id":295270,"name":"Jianming Wang","orcid":"0000-0002-7265-1764","position":5,"is_corresponding":false},{"id":1020210,"name":"Ansu O. Perekatt","orcid":"0000-0003-3083-8405","position":6,"is_corresponding":false},{"id":231842,"name":"Wenwei Hu","orcid":"0000-0003-3971-4257","position":7,"is_corresponding":false},{"id":28520,"name":"Jason R. Spence","orcid":"0000-0001-7869-3992","position":8,"is_corresponding":false},{"id":241177,"name":"Michael P. Verzi","orcid":"0000-0003-4082-4330","position":9,"is_corresponding":false},{"id":506485,"name":"Lei Chen","orcid":"0000-0001-7812-508X","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T01:18:37.743462Z","pmid":"36711781","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}