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 p...

器官发生依赖于由扩张的祖细胞（progenitor cells）池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）研究表明，扩张的胰腺祖细胞最初可分化为所有内分泌细胞、导管细胞与腺泡细胞，但在胚胎第13.5天时便转变为双潜能祖细胞，仅能分化为内分泌细胞与导管细胞。然而，此前尚未有研究阐明单个祖细胞维持自我更新与谱系特异性分化之间平衡的动态过程。本研究借助三维活细胞成像（three-dimensional live imaging）与体内克隆分析（in vivo clonal analysis）技术，揭示了单个细胞对组织整体行为的贡献，并阐明了祖细胞的三种分裂模式：对称自我更新型分裂、对称内分泌源性分裂，以及可生成一个祖细胞与一个内分泌祖细胞的不对称分裂。定量分析结果表明，内分泌分化过程与一种基于细胞周期依赖性随机启动的简化模型相符，原文后续内容存在截断。