| First Author | Ohara TE | Year | 2022 |
| Journal | Dev Cell | Volume | 57 |
| Issue | 2 | Pages | 166-179.e6 |
| PubMed ID | 35016013 | Mgi Jnum | J:322627 |
| Mgi Id | MGI:6871064 | Doi | 10.1016/j.devcel.2021.12.012 |
| Citation | Ohara TE, et al. (2022) Adaptive differentiation promotes intestinal villus recovery. Dev Cell 57(2):166-179.e6 |
| abstractText | Loss of differentiated cells to tissue damage is a hallmark of many diseases. In slow-turnover tissues, long-lived differentiated cells can re-enter the cell cycle or transdifferentiate to another cell type to promote repair. Here, we show that in a high-turnover tissue, severe damage to the differentiated compartment induces progenitors to transiently acquire a unique transcriptional and morphological postmitotic state. We highlight this in an acute villus injury model in the mouse intestine, where we identified a population of progenitor-derived cells that covered injured villi. These atrophy-induced villus epithelial cells (aVECs) were enriched for fetal markers but were differentiated and lineage committed. We further established a role for aVECs in maintaining barrier integrity through the activation of yes-associated protein (YAP). Notably, loss of YAP activity led to impaired villus regeneration. Thus, we define a key repair mechanism involving the activation of a fetal-like program during injury-induced differentiation, a process we term "adaptive differentiation." |
