Tracing the cellular basis of islet specification in mouse pancreas.
Tracing the cellular basis of islet specification in mouse pancreas.
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DOI：
10.1038/s41467-020-18837-3
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发表时间：
2020-10-07
影响因子：
16.6
通讯作者：
Simons BD
中科院分区：
文献类型：
--
作者：
Sznurkowska MK;Hannezo E;Azzarelli R;Chatzeli L;Ikeda T;Yoshida S;Philpott A;Simons BD
胰岛在调节血糖水平中起着重要作用。虽然胰岛细胞分化的分子途径开始被解决，但胰岛形态发生和命运分配的细胞基础仍然不清楚。通过结合无偏倚和有针对性的谱系追踪，我们解决了导致小鼠胰岛形成的事件。通过对多个胚胎时间点诱导的克隆的统计分析，我们发现，在继发性转变过程中，胰岛的形成涉及多个等能内分泌祖细胞的聚集，从细胞分裂的随机扩增阶段过渡到亚谱系限制和有限的胰岛裂变阶段。总之，这些结果定量地解释了成熟胰岛的异质大小分布和多克隆程度，以及胰岛内部和之间祖细胞的分散。此外，我们的研究结果表明，在二次转化过程中，α-和β-细胞以当代方式产生。总之，这些发现提供了对胰岛发育的细胞基础的深入了解。胰岛形态发生和命运分配的细胞基础尚不清楚。在这里，作者使用R26-CreER-R26R-Confetti小鼠系定量跟踪胰岛形成的克隆动力学，显示在继发性转变期间，胰岛祖细胞如何通过几轮随机细胞分裂扩增，然后被限制为α和β细胞亚系。
Pancreatic islets play an essential role in regulating blood glucose level. Although the molecular pathways underlying islet cell differentiation are beginning to be resolved, the cellular basis of islet morphogenesis and fate allocation remain unclear. By combining unbiased and targeted lineage tracing, we address the events leading to islet formation in the mouse. From the statistical analysis of clones induced at multiple embryonic timepoints, here we show that, during the secondary transition, islet formation involves the aggregation of multiple equipotent endocrine progenitors that transition from a phase of stochastic amplification by cell division into a phase of sublineage restriction and limited islet fission. Together, these results explain quantitatively the heterogeneous size distribution and degree of polyclonality of maturing islets, as well as dispersion of progenitors within and between islets. Further, our results show that, during the secondary transition, α- and β-cells are generated in a contemporary manner. Together, these findings provide insight into the cellular basis of islet development. The cellular basis of islet morphogenesis and fate allocation remain unclear. Here, the authors use a R26-CreER-R26R-Confetti mouse line to follow quantitatively the clonal dynamics of islet formation showing how, during the secondary transition, islet progenitors amplify through rounds of stochastic cell division before becoming restricted to α and β cell sublineages.
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体内成像显示成年小鼠肠道中存在隐窝分裂和融合现象
影响因子：
29.4
作者：
Bruens L;Ellenbroek SIJ;van Rheenen J;Snippert HJ
通讯作者：
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作者：
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通讯作者：
Melton, DA
影响因子：
7.7
作者：
Edlund, H
通讯作者：
Edlund, H