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Engineered Glycocalyx Regulates Stem Cell Proliferation in Murine Crypt Organoids
Cell Chemical Biology ( IF 8.6 ) Pub Date : 2018-02-08 , DOI: 10.1016/j.chembiol.2018.01.010
Sara H. Rouhanifard , Aime Lopez Aguilar , Lu Meng , Kelley W. Moremen , Peng Wu

At the base of the intestinal crypt, long-lived Lgr5+stem cells are intercalated by Paneth cells that provide essential niche signals for stem cell maintenance. This unique epithelial anatomy makes the intestinal crypt one of the most accessible models for the study of adult stem cell biology. The glycosylation patterns of this compartment are poorly characterized, and the impact of glycans on stem cell differentiation remains largely unexplored. We find that Paneth cells, but not Lgr5+stem cells, express abundant terminalN-acetyllactosamine (LacNAc). Employing an enzymatic method to edit glycans in cultured crypt organoids, we assess the functional role of LacNAc in the intestinal crypt. We discover that blocking access to LacNAc on Paneth cells leads to hyperproliferation of the neighboring Lgr5+stem cells, which is accompanied by the downregulation of genes that are known as negative regulators of proliferation.

中文翻译:

工程化的糖萼调节鼠隐窝类器官中的干细胞增殖。

在小肠隐窝的底部,长寿的Lgr5 +干细胞被Paneth细胞插入,后者为干细胞的维持提供了必要的利基信号。这种独特的上皮解剖结构使肠道隐窝成为研究成人干细胞生物学的最容易获得的模型之一。该隔室的糖基化模式表征不清,聚糖对干细胞分化的影响仍未得到充分研究。我们发现Paneth细胞,但不是Lgr5 +干细胞,表达大量的终端N-乙酰乳糖胺(LacNAc)。我们采用酶学方法编辑培养的隐窝类器官中的聚糖,我们评估了LacNAc在肠道隐窝中的功能作用。我们发现阻止Paneth细胞访问LacNAc会导致邻近Lgr5 +干细胞过度增殖,
更新日期:2018-04-19
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