Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss
Fabrizio Thorel,Virginie Nepote,Isabelle Avril,Kenji Kohno,Renaud Desgraz,Simona Chera,Pedro Luis Herrera +6 more
TLDR
In this article, a transgenic model of diphtheria-toxin-induced acute selective near-total beta-cell ablation was used to investigate whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total β-cell loss, as in diabetes.Abstract:
Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total beta-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-cell) source. Here we show beta-cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-cell ablation. If given insulin, the mice survived and showed beta-cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-cells before beta-cell ablation tracked large fractions of regenerated beta-cells as deriving from alpha-cells, revealing a previously disregarded degree of pancreatic cell plasticity. Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing beta-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.read more
Citations
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Characterizing pancreatic β-cell heterogeneity in the streptozotocin model by single-cell transcriptomic analysis.
Ye Feng,Wei-Lin Qiu,Xin-Xin Yu,Yu Zhang,Mao-Yang He,Lin-Chen Li,Li Yang,Weiyi Zhang,Michael Franti,Junqing Ye,Joerg D. Hoeck,Cheng-Ran Xu +11 more
TL;DR: The molecular characteristics of islet cells treated with STZ are explored and β-cell dysfunction and regeneration in the STZ model is re-evaluated and the heterogeneity of β-cells is identified in both physiological and pathological conditions.
Journal ArticleDOI
Generation of mouse models for type 1 diabetes by selective depletion of pancreatic beta cells using toxin receptor-mediated cell knockout.
Kunie Matsuoka,Michiko Saito,Kosuke Shibata,Michiko Sekine,Hiroshi Shitara,Choji Taya,Xiaohong Zhang,Tsuneo A. Takahashi,Kenji Kohno,Yoshiaki Kikkawa,Hiromichi Yonekawa +10 more
TL;DR: The high specificity with which DT causes depletion in pancreatic β cells of these Tg mice is highly useful for diabetogenic research.
Journal ArticleDOI
Efficient generation of pancreatic β-like cells from the mouse gallbladder.
TL;DR: Gene expression analysis indicated that rGBC2 clustered closer with β cells and had a metabolic gene expression profile resembling neonatal β cells, which provides further understanding of endodermal lineage conversion and potential for development of cell replacement therapy for type 1 diabetes patients.
Journal ArticleDOI
Islet Regeneration: Endogenous and Exogenous Approaches.
Fiona M. Docherty,Lori Sussel +1 more
TL;DR: Exogenous mechanisms of beta cell regeneration during steady state, stress and disease; efforts to stimulate endogenous regeneration and transdifferentiation; and exogenous methods of Beta cell generation and transplantation are reviewed.
Journal ArticleDOI
Regenerating β cells of the pancreas - potential developments in diabetes treatment.
Shengli Dong,Hongju Wu +1 more
TL;DR: The mechanisms underlying embryonic β cell development and spontaneous adultβ cell regeneration form the basis for developing β cell regeneration strategies, and more hurdles need to be overcome before any of the strategies suggested can be fully translated from bench to bedside.
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Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation.
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