Conversion of Adult Pancreatic α-cells to β-cells After Extreme β-cell Loss
By F. Thorel, V. Népote, I. Avril, K. Kohno, R. Desgraz, S. Chera, P. Herrera. Nature, 2010
961 citations recorded by the source corpus.
Pancreatic insulin-producing β-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, β-cell loss). It is not known whether adult mammals can differentiate (regenerate) new β-cells after extreme, total β-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-β-cell) source. Here we show β-cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total β-cell ablation. If given insulin, the mice survived and showed β-cell mass augmentation with time. Lineage-tracing to label the glucagon-producing α-cells before β-cell ablation tracked large fractions of regenerated β-cells as deriving from α-cells, revealing a previously disregarded degree of pancreatic cell plasticity. Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing β-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.
Subfields: Endocrinology, Diabetes and Metabolism, Genetics, Surgery
View Paper: https://www.semanticscholar.org/paper/34a54ee1ca85558491a1ff5d4ee7f85652eac0fe
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Citations in the corpus
- Pancreatic β-Cell Dedifferentiation As Mechanism Of Diabetic β-Cell Failure (2012, positive): “Our work expands the implications of the increased plasticity of pancreatic endocrine cells observed as a survival mechanism inmodels of extreme b cell ablation (Thorel et al., 2010), by suggesting that plasticity occurs in common forms of b cell dysfunction, and is caused by the downregulation of F”
- Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis (2013, positive): “Lineage tracing studies have demonstrated that these ‘ de novo beta cells’ can be derived from pre-existing beta cells (Dor et al , 2004), or by conversion of alpha cells, after almost 90% beta-cell ablation (Thorel et al , 2010).”
- Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. (2011, neutral): “Such differentiation-state plasticity occurs in response to either genetic or microenvironmental perturbations (Deng et al., 2011; Thorel et al., 2010; Zhou et al., 2008) and has also been observed during normal developmental processes (Richard et al., 2011).”
- Pancreas organogenesis: From bud to plexus to gland (2011, methodology): “Cre-based lineage tracing was used to conclude that under 99% b-cell destruction, a-cells move through a bihormonal glucagonþ/insulinþ state on their way to generate authentic insulinþ b-cells (Thorel et al., 2010).”