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Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells
Cell Stem Cell ( IF 23.9 ) Pub Date : 2017-03-09 00:00:00 , DOI: 10.1016/j.stem.2017.02.007
Francisco M. Barriga , Elisa Montagni , Miyeko Mana , Maria Mendez-Lago , Xavier Hernando-Momblona , Marta Sevillano , Amy Guillaumet-Adkins , Gustavo Rodriguez-Esteban , Simon J.A. Buczacki , Marta Gut , Holger Heyn , Douglas J. Winton , Omer H. Yilmaz , Camille Stephan-Otto Attolini , Ivo Gut , Eduard Batlle

Highly proliferative Lgr5+ stem cells maintain the intestinal epithelium and are thought to be largely homogeneous. Although quiescent intestinal stem cell (ISC) populations have been described, the identity and features of such a population remain controversial. Here we report unanticipated heterogeneity within the Lgr5+ ISC pool. We found that expression of the RNA-binding protein Mex3a labels a slowly cycling subpopulation of Lgr5+ ISCs that contribute to all intestinal lineages with distinct kinetics. Single-cell transcriptome profiling revealed that Lgr5+ cells adopt two discrete states, one of which is defined by a Mex3a expression program and relatively low levels of proliferation genes. During homeostasis, Mex3a+ cells continually shift into the rapidly dividing, self-renewing ISC pool. Chemotherapy and radiation preferentially target rapidly dividing Lgr5+ cells but spare the Mex3a-high/Lgr5+ population, helping to promote regeneration of the intestinal epithelium following toxic insults. Thus, Mex3a defines a reserve-like ISC population within the Lgr5+ compartment.

中文翻译:

Mex3a标志着Lgr5 +肠干细胞的缓慢分裂亚群。

高度增殖的Lgr5 +干细胞可维持肠道上皮,并被认为在很大程度上是同质的。尽管已描述了静态肠道干细胞(ISC)种群,但这种种群的身份和特征仍存在争议。在这里,我们报告了Lgr5 + ISC池内的意外异质性。我们发现,RNA结合蛋白Mex3a的表达标记了Lgr5 + ISC的缓慢循环亚群,这些亚群以不同的动力学参与了所有肠道谱系。单细胞转录组分析显示,Lgr5 +细胞采用两种离散状态,其中一种由Mex3a表达程序和相对较低水平的增殖基因定义。在体内平衡过程中,Mex3a +细胞不断转移到快速分裂,自我更新的ISC库中。化学疗法和放射疗法优先针对快速分裂的Lgr5 +细胞,但不保留Mex3a-high / Lgr5 +高种群,这有助于促进中毒后肠上皮的再生。因此,Mex3a在Lgr5 +区室中定义了类似储备的ISC种群。
更新日期:2017-06-12
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