Murine pancreatic endocrinogenesis has been extensively studied, but human data remain scarce due to limited sample availability. Here, we first built a large collection of human embryonic and fetal pancreases covering the first trimester of pregnancy to explore human endocrinogenesis. Using an experimental pipeline combining in toto staining, tissue clearing, and light-sheet fluorescence microscopy, we show that insulin+, glucagon+, and somatostatin+ cells appear simultaneously at Carnegie Stage (CS) 16. This contrasts with rodents where glucagon+ cells appear first, followed by insulin+ and finally somatostatin+ cells and highlights interspecies differences. We also detected bi-hormonal endocrine cells in 7 out of 9 human pancreases between CS16-18, which were no longer detected at later stages. We observed that cell distribution within human fetal islets resembles adult mouse islets, with a core of beta cells surrounded by alpha and delta cells, differing from a more complex arrangement in adult human islets. This, in connection with the small size of human fetal islets when compared to adult, suggests that adult human islets may form by fusion of pre-existing islets, in contrast to the mouse fission model. Together, our study provides a detailed and comprehensive description of the spatiotemporal dynamics of human pancreatic endocrinogenesis.

中文翻译：

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产前早期人类胰腺内分泌生成的影像学检查


小鼠胰腺内分泌发生已被广泛研究，但由于样本可用性有限，人类数据仍然稀缺。在这里，我们首先构建了大量涵盖妊娠早期的人胚胎和胎儿胰腺，以探索人类内分泌发生。使用结合 toto 染色、组织透明化和光片荧光显微镜的实验管道，我们表明胰岛素 + 、胰高血糖素 + 和生长抑素 + 细胞同时出现在卡内基阶段 （CS） 16。这与啮齿动物形成鲜明对比，胰高血糖素 + 细胞首先出现，然后是胰岛素 +，最后是生长抑素 + 细胞，并突出了种间差异。我们还在 CS16-18 之间的 9 个人胰腺中有 7 个检测到双激素内分泌细胞，这些细胞在后期不再检测到。我们观察到人类胎岛内的细胞分布类似于成年小鼠胰岛，β 细胞的核心被 α 和 delta 细胞包围，这与成人胰岛中更复杂的排列不同。这与人类胎儿胰岛的体积与成人相比较小有关，表明与小鼠裂变模型相反，成人人类胰岛可能是通过预先存在的胰岛融合形成的。总之，我们的研究提供了对人类胰腺内分泌发生的时空动力学的详细而全面的描述。