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| Item Type: | Article |
|---|---|
| Title: | Extrusion of BMP2+ surface colonocytes promotes stromal remodeling and tissue regeneration |
| Creators Name: | Heuberger, J., Liu, L., Berger, H., van den Heuvel, J., Lin, M., Müllerke, S., Bayram, S., Beccaceci, G., de Jonge, H., Gherardi, E. and Sigal, M. |
| Abstract: | The colon epithelium frequently incurs damage through toxic influences. Repair is rapid, mediated by cellular plasticity and acquisition of the highly proliferative regenerative state. However, the mechanisms that promote the regenerative state are not well understood. Here, we reveal that upon injury and subsequent inflammatory response, IFN-γ drives widespread epithelial remodeling. IFN-γ promotes rapid apoptotic extrusion of fully differentiated surface colonocytes, while simultaneously causing differentiation of crypt-base stem and progenitor cells towards a colonocyte-like lineage. However, unlike homeostatic colonocytes, these IFN-γ-induced colonocytes neither respond to nor produce BMP-2 but retain regenerative capacity. The reduction of BMP-2-producing epithelial surface cells causes a remodeling of the surrounding mesenchymal niche, inducing high expression of HGF, which promotes proliferation of the IFN-γ-induced colonocytes. This mechanism of lineage replacement and subsequent remodeling of the mesenchymal niche enables tissue-wide adaptation to injury and efficient repair. |
| Keywords: | Apoptosis, Bone Morphogenetic Protein 2, Cell Differentiation, Cell Proliferation, Colon, Epithelial Cells, Interferon-Gamma, Intestinal Mucosa, Inbred C57BL Mice, Regeneration, Stromal Cells, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 16 |
| Number: | 1 |
| Page Range: | 4131 |
| Date: | 3 May 2025 |
| Official Publication: | https://doi.org/10.1038/s41467-025-59474-y |
| PubMed: | View item in PubMed |
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