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  Adult duct-lining cells can reprogram into β-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., et al. (2013). Adult duct-lining cells can reprogram into β-like cells able to counter repeated cycles of toxin-induced diabetes. Developmental Cell, 26(1), 86-100. doi:10.1016/j.devcel.2013.05.018.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-3C2F-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-95F4-8
Genre: Journal Article

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Al-Hasani, K., Author
Pfeifer, A., Author
Courtney, M., Author
Ben-Othman, N., Author
Gjernes, E., Author
Vieira, A., Author
Druelle, N., Author
Avolio, F., Author
Ravassard, P., Author
Leuckx, G., Author
Lacas-Gervais, S., Author
Ambrosetti, D., Author
Benizri, E., Author
Hecksher-Sorensen, J., Author
Gounon, P., Author
Ferrer, J., Author
Gradwohl, G., Author
Heimberg, H., Author
Mansouri, A.1, Author              
Collombat, P., Author
Affiliations:
1Research Group of Molecular Cell Differentiation, MPI for biophysical chemistry, Max Planck Society, ou_578588              

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 Abstract: It was recently demonstrated that embryonic glucagon-producing cells in the pancreas can regenerate and convert into insulin-producing β-like cells through the constitutive/ectopic expression of the Pax4 gene. However, whether α 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 β-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 α-to-β-like cell conversion, pancreatic duct-lining precursor cells are continuously mobilized, re-express the developmental gene Ngn3, and successively adopt a glucagon+ and a β-like cell identity through a mechanism involving the reawakening of the epithelial-to-mesenchymal transition. Importantly, these processes can repeatedly regenerate the whole β cell mass and thereby reverse several rounds of toxin-induced diabetes, providing perspectives to design therapeutic regenerative strategies.

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Language(s): eng - English
 Dates: 2013-06-27
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.devcel.2013.05.018
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Title: Developmental Cell
Source Genre: Journal
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Pages: - Volume / Issue: 26 (1) Sequence Number: - Start / End Page: 86 - 100 Identifier: -