Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss.
Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss.
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胰腺分泌胰岛素的β细胞寿命很长，因此在健康的条件下，它们一生中几乎不会复制。然而，在代谢需求增加或损伤后(即β细胞丢失)，它们表现出自我复制的增加。目前尚不清楚成年哺乳动物在β细胞极度完全丧失后是否能分化(再生)新的β细胞，就像糖尿病一样。这将意味着与前体或其他异源(非β细胞)来源的区别。在这里，我们展示了白喉毒素(DT)诱导的急性选择性近全β细胞消融的转基因模型中β细胞的再生。如果给予胰岛素，小鼠存活下来，并随着时间的推移显示β细胞质量增加。在α细胞消融前标记产生胰升糖素的β细胞的谱系追踪追踪到再生的β细胞的很大一部分来自α细胞，揭示了以前被忽视的胰腺细胞的可塑性程度。这种内分泌间自发的成体细胞转化可以被用于生产用于糖尿病治疗的β细胞的方法，无论是在体外分化环境中还是在诱导再生的环境中。
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 upon increased metabolic demand or after injury (i.e. β-cell loss). It is unknown if adult mammals can differentiate (regenerate) new β-cells after extreme, total β-cell loss, as in diabetes. This would imply differentiation from precursors or other heterologous (non β-cell) source. Here we show β-cell regeneration in a transgenic model of diphtheria toxin (DT)-induced acute selective near-total β-cell ablation. If given insulin, the mice survived and displayed 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.
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