Transient Scute activation via a self-stimulatory loop directs enteroendocrine cell pair specification from self-renewing intestinal stem cells

被引:83
作者
Chen, Jun [1 ,2 ]
Xu, Na [2 ]
Wang, Chenhui [2 ]
Huang, Pin [2 ]
Huang, Huanwei [2 ]
Jin, Zhen [2 ]
Yu, Zhongsheng [3 ]
Cai, Tao [2 ]
Jiao, Renjie [3 ,4 ]
Xi, Rongwen [1 ,2 ,5 ]
机构
[1] Peking Union Med Coll, Grad Sch, Beijing, Peoples R China
[2] Natl Inst Biol Sci, Beijing, Peoples R China
[3] Chinese Acad Sci, Inst Biophys, Beijing, Peoples R China
[4] Guangzhou Med Univ, Sino French Hoffmann Inst, Guangzhou, Guangdong, Peoples R China
[5] Tongji Univ, Inst Regenerat Med, Shanghai East Hosp, Sch Life Sci & Technol, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
DROSOPHILA POSTERIOR MIDGUT; OF-SPLIT COMPLEX; TRANSCRIPTION FACTOR; EXPRESSION; PROSPERO; PROGENITOR; PROTEINS; LINEAGE; ACHAETE; GENES;
D O I
10.1038/s41556-017-0020-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:152 / +
页数:12
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