Adult Duct-Lining Cells Can Reprogram into beta-like Cells Able to Counter Repeated Cycles of Toxin-Induced Diabetes
2013 | journal article. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
Adult Duct-Lining Cells Can Reprogram into beta-like Cells Able to Counter Repeated Cycles of Toxin-Induced Diabetes
Al-Hasani, K.; Pfeifer, A.; Courtney, M.; Ben-Othman, N.; Gjernes, E.; Vieira, A. & Druelle, N. et al. (2013)
Developmental Cell, 26(1) pp. 86-100. DOI: https://doi.org/10.1016/j.devcel.2013.05.018
Documents & Media
Details
- Authors
- Al-Hasani, Keith; Pfeifer, Anja; Courtney, Monica; Ben-Othman, Nouha; Gjernes, Elisabet; Vieira, Andhira; Druelle, Noemie; Avolio, Fabio; Ravassard, Philippe; Leuckx, Gunter; Lacas-Gervais, Sandra; Ambrosetti, Damien; Benizri, Emmanuel; Hecksher-Sorensen, Jacob; Gounon, Pierre; Ferrer, Jorge; Gradwohl, Gerard; Heimberg, Harry; Mansouri, Ahmed; Collombat, Patrick
- Abstract
- It was recently demonstrated that embryonic glucagon-producing cells in the pancreas can regenerate and convert into insulin-producing beta-like cells through the constitutive/ectopic expression of the Pax4 gene. However, whether alpha cells in adult mice display the same plasticity is unknown. Similarly, the mechanisms underlying such reprogramming remain unclear. We now demonstrate that the misexpression of Pax4 in glucagon(+) cells age-independently induces their conversion into beta-like cells and their glucagon shortage-mediated replacement, resulting in islet hypertrophy and in an unexpected islet neogenesis. Combining several lineage-tracing approaches, we show that, upon Pax4-mediated alpha-to-beta-like cell conversion, pancreatic duct-lining precursor cells are continuously mobilized, re-express the developmental gene Ngn3, and successively adopt a glucagon+ and a beta-like cell identity through a mechanism involving the reawakening of the epithelial-to-mesenchymal transition. Importantly, these processes can repeatedly regenerate the whole beta cell mass and thereby reverse several rounds of toxin-induced diabetes, providing perspectives to design therapeutic regenerative strategies.
- Issue Date
- 2013
- Status
- published
- Publisher
- Cell Press
- Journal
- Developmental Cell
- ISSN
- 1534-5807