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Transient Scute activation via a self-stimulatory loop directs enteroendocrine cell pair specification from self-renewing intestinal stem cells.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2018-Feb-01 , DOI: 10.1038/s41556-017-0020-0
Jun Chen , Na Xu , Chenhui Wang , Pin Huang , Huanwei Huang , Zhen Jin , Zhongsheng Yu , Tao Cai , Renjie Jiao , Rongwen Xi

The process through which multiple types of cell-lineage-restricted progenitor cells are specified from multipotent stem cells is unclear. Here we show that, in intestinal stem cell lineages in adult Drosophila, in which the Delta-Notch-signalling-guided progenitor cell differentiation into enterocytes is the default mode, the specification of enteroendocrine cells (EEs) is initiated by transient Scute activation in a process driven by transcriptional self-stimulation combined with a negative feedback regulation between Scute and Notch targets. Scute activation induces asymmetric intestinal stem cell divisions that generate EE progenitor cells. The mitosis-inducing and fate-inducing activities of Scute guide each EE progenitor cell to divide exactly once prior to its terminal differentiation, yielding a pair of EEs. The transient expression of a fate inducer therefore specifies both type and numbers of committed progenitor cells originating from stem cells, which could represent a general mechanism used for diversifying committed progenitor cells from multipotent stem cells.

中文翻译:

通过自我刺激环的瞬时Scute激活从自我更新的肠干细胞引导肠内分泌细胞对规范。

从多能干细胞中指定多种类型的受细胞系限制的祖细胞的过程尚不清楚。在这里,我们显示,在成年果蝇的肠道干细胞谱系中,其中将Delta-Notch信号引导的祖细胞分化为肠上皮细胞是默认模式,肠内分泌细胞(EEs)的规范是通过在小鼠体内短暂的Scute激活而启动转录自我刺激与Scute和Notch目标之间的负反馈调节相结合而驱动的过程。扇形激活会诱导不对称的肠道干细胞分裂,从而产生EE祖细胞。Scute的有丝分裂诱导和命运诱导活动引导每个EE祖细胞在其终末分化之前精确地分裂一次,从而产生一对EE。
更新日期:2018-01-15
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