| First Author | Chen L | Year | 2023 |
| Journal | Cell Stem Cell | Volume | 30 |
| Issue | 11 | Pages | 1520-1537.e8 |
| PubMed ID | 37865088 | Mgi Jnum | J:342163 |
| Mgi Id | MGI:7546699 | Doi | 10.1016/j.stem.2023.09.015 |
| Citation | Chen L, et al. (2023) TGFB1 induces fetal reprogramming and enhances intestinal regeneration. Cell Stem Cell 30(11):1520-1537.e8 |
| abstractText | The gut epithelium has a remarkable ability to recover from damage. We employed a combination of high-throughput sequencing approaches, mouse genetics, and murine and human organoids 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. The depletion of macrophages or genetic disruption of TGFB signaling significantly impaired the regenerative response. Intestinal regeneration is characterized by the induction of a fetal-like transcriptional signature during repair. In organoid culture, TGFB1 treatment was necessary and sufficient to induce the fetal-like/regenerative state. Mesenchymal cells were also responsive to TGFB1 and enhanced the regenerative response. Mechanistically, pro-regenerative factors, YAP/TEAD and SOX9, are activated in the 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 cellular therapy. |
