Department of Genetic Medicine & Development, iGE3 and Centre Facultaire du Diabète, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
Touchstone Diabetes Center, Departments of Internal Medicine and Cell Biology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8549, USA.
Cell Rep. 2022 Feb 15;38(7):110377. doi: 10.1016/j.celrep.2022.110377.
The precise developmental dynamics of the pancreatic islet endocrine cell types, and their interrelation, are unknown. Some authors claim the persistence of islet cell differentiation from precursor cells after birth ("neogenesis"). Here, using four conditional cell lineage tracing ("pulse-and-chase") murine models, we describe the natural history of pancreatic islet cells, once they express a hormone gene, until late in life. Concerning the contribution of early-appearing embryonic hormone-expressing cells to the formation of islets, we report that adult islet cells emerge from embryonic hormone-expressing cells arising at different time points during development, without any evidence of postnatal neogenesis. We observe specific patterns of hormone gene activation and switching during islet morphogenesis, revealing that, within each cell type, cells have heterogeneous developmental trajectories. This likely applies to most maturating cells in the body, and explains the observed phenotypic variability within differentiated cell types. Such knowledge should help devising novel regenerative therapies.
胰腺胰岛内分泌细胞类型的确切发育动态及其相互关系尚不清楚。一些作者声称胰岛细胞分化自出生前的前体细胞（“新生”）。在这里，我们使用四种条件细胞谱系追踪（“脉冲和追踪”）小鼠模型，描述了一旦表达激素基因的胰岛细胞的自然史，直到生命后期。关于早期出现的胚胎激素表达细胞对胰岛形成的贡献，我们报告说，成年胰岛细胞来自于在发育过程中不同时间点出现的胚胎激素表达细胞，没有任何证据表明有后天的新生。我们观察到胰岛形态发生过程中激素基因激活和转换的特定模式，表明在每种细胞类型中，细胞具有异质的发育轨迹。这可能适用于体内大多数成熟细胞，并解释了分化细胞类型中观察到的表型变异性。这种知识应该有助于设计新的再生治疗方法。
