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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Journal ArticleDOI
TCF7L2 promotes beta cell regeneration in human and mouse pancreas
Luan Shu,K. S. Zien,G. Gutjahr,Jose Oberholzer,François Pattou,Julie Kerr-Conte,Kathrin Maedler +6 more
TL;DR: The present study demonstrates that TCF7L2 overexpression fosters beta cell regeneration and implies correlation of TCF 7L2 levels and new beta cell formation.
Journal ArticleDOI
Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo
Taka-aki Matsuoka,Satoshi Kawashima,Takeshi Miyatsuka,Takeshi Miyatsuka,Shugo Sasaki,Naoki Shimo,Naoto Katakami,Dan Kawamori,Satomi Takebe,Pedro Luis Herrera,Hideaki Kaneto,Roland Stein,Iichiro Shimomura +12 more
TL;DR: Transgenic mice conditionally expressing the islet β-cell–enriched Mafa and/or Pdx1 transcription factors are generated to examine their potential to transdifferentiate embryonic pan–islet cell Ngn3-positive progenitors and the later glucagon-positive α-cell population into β-cells.
Journal ArticleDOI
Human duct cells contribute to β cell compensation in insulin resistance
Ercument Dirice,Ercument Dirice,Dario F. De Jesus,Dario F. De Jesus,Dario F. De Jesus,Sevim Kahraman,Sevim Kahraman,Giorgio Basile,Giorgio Basile,Raymond W.S. Ng,Raymond W.S. Ng,Abdelfattah El Ouaamari,Abdelfattah El Ouaamari,Adrian Kee Keong Teo,Adrian Kee Keong Teo,Shweta Bhatt,Shweta Bhatt,Jiang Hu,Jiang Hu,Rohit N. Kulkarni,Rohit N. Kulkarni,Rohit N. Kulkarni +21 more
TL;DR: During increased insulin demand, ductal cells contribute to the compensatory β cell pool by differentiation/neogenesis, and are identified in pancreas sections from pregnant humans and in individuals with T2D.
Journal ArticleDOI
Fate specification in the adult brain – lessons for eliciting neurogenesis from glial cells
Jovica Ninkovic,Magdalena Götz +1 more
TL;DR: A model of fate specification is proposed identifying the states of easiest transition between glio- and neurogenesis, highlighting the unique mechanisms stabilising the neural stem cell state.
Journal ArticleDOI
INS-1 Cells Undergoing Caspase-Dependent Apoptosis Enhance the Regenerative Capacity of Neighboring Cells
Caroline Bonner,Siobhan Bacon,Caoimhín G. Concannon,S. R. Rizvi,Mathurin Baquié,Angela M. Farrelly,Seán M. Kilbride,Heiko Düssmann,Manus W. Ward,Chantal M. Boulanger,Claes B. Wollheim,Rolf Graf,Maria M. Byrne,Jochen H. M. Prehn +13 more
TL;DR: The results suggest that apoptosing INS-1 cells shed microparticles that may stimulate PSP/reg induction in neighboring cells, a mechanism that may facilitate the recovery of β-cell mass in HNF1A-MODY.
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Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation.
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Journal ArticleDOI
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