工程化糖萼调控鼠类隐窝类器官中干细胞的增殖。
Engineered Glycocalyx Regulates Stem Cell Proliferation in Murine Crypt Organoids.
机构信息
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
出版信息
Cell Chem Biol. 2018 Apr 19;25(4):439-446.e5. doi: 10.1016/j.chembiol.2018.01.010. Epub 2018 Feb 8.
Abstract
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 terminal N-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.
摘要
在肠隐窝的底部，长寿的 Lgr5 干细胞被 Paneth 细胞插入，Paneth 细胞为干细胞维持提供必要的生态位信号。这种独特的上皮解剖结构使肠隐窝成为研究成人干细胞生物学的最易接近的模型之一。该隔室的糖基化模式描述得很差，糖对干细胞分化的影响在很大程度上仍未得到探索。我们发现 Paneth 细胞（但不是 Lgr5 干细胞）表达丰富的末端 N-乙酰乳糖胺（LacNAc）。我们采用酶法编辑培养的隐窝类器官中的聚糖，评估 LacNAc 在肠隐窝中的功能作用。我们发现，阻断 Paneth 细胞上 LacNAc 的进入会导致相邻的 Lgr5 干细胞过度增殖，这伴随着已知作为增殖负调节剂的基因下调。
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本文引用的文献
1
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Angew Chem Int Ed Engl. 2018 Jan 22;57(4):967-971. doi: 10.1002/anie.201706535. Epub 2018 Jan 2.
2
Organoids: a Special Issue.类器官：特刊
Development. 2017 Mar 15;144(6):935-937. doi: 10.1242/dev.150292.
3
Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease.培养人类肠道干细胞用于炎症性肠病治疗中的再生应用。
EMBO Mol Med. 2017 May;9(5):558-570. doi: 10.15252/emmm.201607260.
4
Towards understanding microvillus inclusion disease.迈向对微绒毛包涵体病的理解。
Mol Cell Pediatr. 2016 Dec;3(1):3. doi: 10.1186/s40348-016-0031-0. Epub 2016 Jan 29.
5
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Blood. 2015 Feb 26;125(9):1502-6. doi: 10.1182/blood-2014-10-603449. Epub 2014 Nov 26.
6
CHoMP: a chemoenzymatic histology method using clickable probes.CHoMP：一种使用可点击探针的化学酶组织学方法。
Chembiochem. 2014 Dec 15;15(18):2667-73. doi: 10.1002/cbic.201402433. Epub 2014 Nov 17.
7
Monitoring dynamic glycosylation in vivo using supersensitive click chemistry.使用超灵敏点击化学在体内监测动态糖基化。
Bioconjug Chem. 2014 Apr 16;25(4):698-706. doi: 10.1021/bc400502d. Epub 2014 Mar 14.
8
Altered mucus glycosylation in core 1 O-glycan-deficient mice affects microbiota composition and intestinal architecture.核心 1 O-聚糖缺陷型小鼠中黏液糖基化的改变影响肠道微生物组成和肠道结构。
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PLoS One. 2013 Dec 5;8(12):e79883. doi: 10.1371/journal.pone.0079883. eCollection 2013.
10
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