Adult Duct-Lining Cells Can Reprogram into ¦Â-like Cells Able to Counter Repeated Cycles of Toxin-Induced Diabetes

详细信息    查看全文

• 作者：Keith Al-Hasani ; Anja Pfeifer ; Monica Courtney ; Nouha Ben-Othman ; Elisabet Gjernes ; Andhira Vieira ; No¨¦mie Druelle ; Fabio Avolio ; Philippe Ravassard ; Gunter Leuckx ; S ; ra Lacas-Gervais ; Damien Ambrosetti ; Emmanuel Benizri ; Jacob Hecksher-Sorensen ; Pierre Gounon ; Jorge Ferrer ; Gerard Gradwohl ; Harry Heimberg ; Ahmed Mansouri ; Patrick Collombat ; et al.
• 刊名：Developmental Cell
• 出版年：2013
• 出版时间：15 July, 2013
• 年：2013
• 卷：26
• 期：1
• 页码：86-100
• 全文大小：8821 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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