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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Book ChapterDOI
Differentiation of Human Embryonic Stem Cells into Pancreatic Endocrine Cells
TL;DR: Functional islet-like endocrine cells have been generated that express key markers of mature pancreatic β-cells, respond to both meal and glucose challenges, and are capable of reversing diabetes in mice.
Journal ArticleDOI
Conversion of pancreatic α cells into insulin-producing cells modulated by β-cell insufficiency and supplemental insulin administration.
Takehiro Katahira,Takeshi Miyatsuka,Masaki Miura,Luka Suzuki,Miwa Himuro,Yuya Nishida,Hiroaki Satoh,Hirotaka Watada +7 more
TL;DR: Adult α cells have plasticity, which enables them to be reprogrammed into insulin-producing cells under diabetic conditions, and this can be modulated by supplemental insulin administration.
Journal ArticleDOI
Deciphering the origins and fates of steroidogenic lineages in the mouse testis.
Herta Ademi,Cyril Djari,Chloé Mayère,Yasmine Neirijnck,Pauline Sararols,Chris M Rands,Isabelle Stévant,Béatrice Conne,Serge Nef +8 more
TL;DR: In this paper , in-vivo lineage tracing indicates that Wnt5a-expressing cells are bona fide progenitors of peritubular myoid cells (PMCs), contributing to most of the LCs present in the fetal and adult testis.
Journal ArticleDOI
Cell-based therapy of diabetes: what are the new sources of beta cells?
TL;DR: In this article, different strategies to obtain other sources of islet beta cells are discussed and different strategies for transplanting adult pancreatic islets into type 1 diabetic patients are discussed.
Journal ArticleDOI
Reprogramming of enteroendocrine K cells to pancreatic β-cells through the combined expression of Nkx6.1 and Neurogenin3, and reaggregation in suspension culture.
TL;DR: It is demonstrated that K cells could be reprogrammed partially to β-cells through the combined expression of Nkx6.1 and Neurogenin3, and reaggregation in suspension culture.
References
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Book
Manipulating the mouse embryo: A laboratory manual
TL;DR: Here are recorded the tech- niques for preparing, inserting and analysing DNA sequences, for retroviral infection of mice, for production and use of EC and EK cells as vehicles for engineered sequences and for nuclear transplantation - all against a background of the basic procedures required for pro- ducing and handling the em- bryos.
Journal ArticleDOI
Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
Shankar Srinivas,Tomoko Watanabe,Chyuan-Sheng Lin,Chris M William,Yasuto Tanabe,Thomas M. Jessell,Frank Costantini +6 more
TL;DR: In contrast to existing lacZ reporter lines, where lacZ expression cannot easily be detected in living tissue, the EYFP and ECFP reporter strains are useful for monitoring the expression of Cre and tracing the lineage of these cells and their descendants in cultured embryos or organs.
Journal ArticleDOI
Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation.
TL;DR: This work introduces a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest and suggests that terminally differentiated β-cells retain a significant proliferative capacity in vivo and casts doubt on the idea that adult stem cells have a significant role in β-cell replenishment.
Journal ArticleDOI
In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.
TL;DR: This study identifies a specific combination of three transcription factors (Ngn3) Pdx1 and Mafa that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble β-cells, and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.
Journal ArticleDOI
Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats.
TL;DR: It is reported that exendin-4, a long-acting GLP-I agonist, stimulates both the differentiation of beta-cells from ductal progenitor cells (neogenesis) and proliferation of Beta-cells when administered to rats and holds promise as a novel therapy to stimulate beta-cell growth and differentiation when administer to diabetic individuals with reduced beta- cell mass.
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