Data from: Cell cycle-dependent differentiation dynamics balances growth and endocrine differentiation in the pancreas

Organogenesis relies on the spatiotemporal balancing of differentiation and proliferation driven by an expanding pool of progenitor cells. In the mouse pancreas, lineage tracing at the population level has shown that the expanding pancreas progenitors can initially give rise to all endocrine, ductal, and acinar cells but become bipotent by embryonic day 13.5, giving rise to endocrine cells and ductal cells. However, the dynamics of individual progenitors balancing self-renewal and lineage-specific differentiation has never been described. Using three-dimensional live imaging and in vivo clonal analysis, we reveal the contribution of individual cells to the global behaviour and demonstrate three modes of progenitor divisions: symmetric renewing, symmetric endocrinogenic, and asymmetric generating a progenitor and an endocrine progenitor. Quantitative analysis shows that the endocrine differentiation process is consistent with a simple model of cell cycle–dependent stochastic priming of progenitors to endocrine fate. The findings provide insights to define control parameters to optimize the generation of β-cells in vitro.

器官发生（organogenesis）依赖于扩增的祖细胞（progenitor cells）库所驱动的分化与增殖的时空动态平衡。在小鼠胰腺中，群体水平的谱系示踪（lineage tracing）研究显示，扩增的胰腺祖细胞最初可分化为所有内分泌、导管及腺泡细胞，但在胚胎发育第13.5天时便转变为双潜能状态，仅能分化为内分泌细胞与导管细胞。然而，此前尚未有关于单个祖细胞平衡自我更新与谱系特异性分化的动态过程的相关报道。本研究借助三维活细胞成像与体内克隆分析技术，揭示了单个细胞对整体行为的贡献，并证实了祖细胞存在三种分裂模式：对称自我更新型、对称内分泌源性型，以及可产生一个祖细胞与一个内分泌祖细胞的不对称分裂型。定量分析结果表明，内分泌分化过程与一个基于细胞周期依赖性随机预编程祖细胞朝向内分泌细胞命运的简化模型相符。本研究结果为确定体外优化β细胞（β-cells）生成的调控参数提供了理论参考。