| First Author | Liu CY | Year | 2023 |
| Journal | Dev Cell | Volume | 58 |
| Issue | 21 | Pages | 2309-2325.e7 |
| PubMed ID | 37652012 | Mgi Jnum | J:350794 |
| Mgi Id | MGI:7548243 | Doi | 10.1016/j.devcel.2023.08.011 |
| Citation | Liu CY, et al. (2023) Wound-healing plasticity enables clonal expansion of founder progenitor cells in colitis. Dev Cell 58(21):2309-2325.e7 |
| abstractText | Chronic colonic injury and inflammation pose high risks for field cancerization, wherein injury-associated mutations promote stem cell fitness and gradual clonal expansion. However, the long-term stability of some colitis-associated mutational fields could suggest alternate origins. Here, studies of acute murine colitis reveal a punctuated mechanism of massive, neutral clonal expansion during normal wound healing. Through three-dimensional (3D) imaging, quantitative fate mapping, and single-cell transcriptomics, we show that epithelial wound repair begins with the loss of structural constraints on regeneration, forming fused labyrinthine channels containing epithelial cells reprogrammed to a non-proliferative plastic state. A small but highly proliferative set of epithelial founder progenitor cells (FPCs) subsequently emerges and undergoes extensive cell division, enabling fluid-like lineage mixing and spreading across the colonic surface. Crypt budding restores the glandular organization, imprinting the pattern of clonal expansion. The emergence and functions of FPCs within a critical window of plasticity represent regenerative targets with implications for preneoplasia. |
