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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Regeneration of Amputated Zebrafish Fin Rays from De Novo Osteoblasts
TL;DR: Determining the cellular source of new skeletal elements is critical for understanding appendage regeneration in amphibians and fish and it is revealed that de novo osteoblasts can fully support the regeneration of amputated zebrafish fins.
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De novo formation of the biliary system by TGFβ-mediated hepatocyte transdifferentiation
Johanna R. Schaub,Kari A. Huppert,Simone N. T. Kurial,Bernadette Y. Hsu,Ashley Cast,Bryan Donnelly,Rebekah Karns,Feng Chen,Milad Rezvani,Hubert Y. Luu,Aras N. Mattis,Anne-Laure Rougemont,Philip J. Rosenthal,Stacey S. Huppert,Stacey S. Huppert,Holger Willenbring +15 more
TL;DR: It is shown that transdifferentiation of hepatocytes in the mouse liver can build a structure that failed to form in development—the biliary system in a mouse model that mimics the hepatic phenotype of human Alagille syndrome, and TGFβ signalling is identified as the driver of this compensatory mechanism.
Journal ArticleDOI
Extensive conversion of hepatic biliary epithelial cells to hepatocytes after near total loss of hepatocytes in zebrafish.
TL;DR: A zebrafish model of liver regeneration in which the extent of hepatocyte ablation can be controlled is established, and BECs contribute to regenerating hepatocytes after substantial hepatocyte depletion in zebra fish, thereby leading to recovery from severe liver damage.
Journal ArticleDOI
Reversible changes in pancreatic islet structure and function produced by elevated blood glucose
Melissa F. Brereton,Michaela Iberl,Kenju Shimomura,Quan Zhang,Alice E. Adriaenssens,Peter Proks,Ioannis Spiliotis,William Dace,Katia K. Mattis,Reshma Ramracheya,Fiona M. Gribble,Frank Reimann,Anne Clark,P Rorsman,Frances M. Ashcroft +14 more
TL;DR: This paper showed that β-cell-specific expression of a human activating KATP channel mutation in adult mice leads to rapid diabetes and marked alterations in islet morphology, ultrastructure and gene expression.
Journal ArticleDOI
Lineage tracing reveals the dynamic contribution of Hes1+ cells to the developing and adult pancreas
Daniel Kopinke,Marisa Brailsford,Jill E. Shea,Rebecca Leavitt,Courtney L. Scaife,L. Charles Murtaugh +5 more
TL;DR: A mouse Hes1CreERT2 knock-in allele to inducibly mark Hes1+ cells and their descendants is developed and found that Hes1 expression in the early embryonic pancreas identifies multipotent, Notch-responsive progenitors, differentiation of which is blocked by activated Notch.
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