Bechard Matthew E, Bankaitis Eric D, Ustione Alessandro, Piston David W, Magnuson Mark A, Wright Christopher V E
Department of Cell and Developmental Biology, Vanderbilt Center for Stem Cell Biology, Vanderbilt University School of Medicine, Vanderbilt University Program in Developmental Biology, Nashville, Tennessee.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Genesis. 2017 Sep;55(9). doi: 10.1002/dvg.23050.
During pancreas organogenesis, Neurog3 endocrine-committing cells are generated from a population of Sox9 mitotic progenitors with only a low level of Neurog3 transcriptional activity (Neurog3 ). Low-level Neurog3 protein, in Neurog3 cells, is required to maintain their mitotic endocrine-lineage-primed status. Herein, we describe a Neurog3-driven FUCCI cell-cycle reporter (Neurog3 ) derived from a Neurog3 BAC transgenic reporter that functions as a loxed cassette acceptor (LCA). In cycling Sox9 Neurog3 progenitors, the majority of cells in S-G -M phases have undetectable levels of Neurog3 with increased expression of endocrine progenitor markers, while those in G have low Neurog3 levels with increased expression of endocrine differentiation markers. These findings support a model in which variations in Neurog3 protein levels are coordinated with cell-cycle phase progression in Neurog3 progenitors with entrance into G triggering a concerted effort, beyond increasing Neurog3 levels, to maintain an endocrine-lineage-primed state by initiating expression of the downstream endocrine differentiation program prior to endocrine-commitment.
在胰腺器官发生过程中，Neurog3内分泌定向细胞由一群Sox9有丝分裂祖细胞产生，这些祖细胞仅具有低水平的Neurog3转录活性（Neurog3低水平）。Neurog3细胞中的低水平Neurog3蛋白是维持其有丝分裂内分泌谱系启动状态所必需的。在此，我们描述了一种源自Neurog3 BAC转基因报告基因的Neurog3驱动的FUCCI细胞周期报告基因（Neurog3），其作为一个loxed盒式受体（LCA）发挥作用。在循环的Sox9 Neurog3祖细胞中，处于S-G-M期的大多数细胞Neurog3水平检测不到，而内分泌祖细胞标志物的表达增加，而处于G期的细胞Neurog3水平较低，内分泌分化标志物的表达增加。这些发现支持了一种模型，即Neurog3蛋白水平的变化与Neurog3祖细胞中的细胞周期阶段进展相协调，进入G期会引发协同作用，除了增加Neurog3水平外，还通过在内分泌定向之前启动下游内分泌分化程序的表达来维持内分泌谱系启动状态。
