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Major signaling pathways in intestinal stem cells
Authors:Tim Vanuytsel  Stefania Senger  Alessio Fasano  Terez Shea-Donohue
Institution:1. Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, MD, USA;2. Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Belgium
Abstract:

Background

The discovery of markers to identify the intestinal stem cell population and the generation of powerful transgenic mouse models to study stem cell physiology have led to seminal discoveries in stem cell biology.

Scope of review

In this review we give an overview of the current knowledge in the field of intestinal stem cells (ISCs) highlighting the most recent progress on markers defining the ISC population and pathways governing intestinal stem cell maintenance and differentiation. Furthermore we review their interaction with other stem cell related pathways. Finally we give an overview of alteration of these pathways in human inflammatory gastrointestinal diseases.

Major conclusions

We highlight the complex network of interactions occurring among different pathways and put in perspective the many layers of regulation that occur in maintaining the intestinal homeostasis.

General significance

Understanding the involvement of ISCs in inflammatory diseases can potentially lead to new therapeutic approaches to treat inflammatory GI pathologies such as IBD and celiac disease and could reveal the molecular mechanisms leading to the pathogenesis of dysplasia and cancer in inflammatory chronic conditions. This article is part of a Special Issue entitled Biochemistry of Stem Cells.
Keywords:GI  gastrointestinal  BrdU  bromodeoxyuridine  LRC  label-retaining cells  CBC  crypt base columnar cells  ISC  intestinal stem cell  DSS  dextran sodium sulfate  KO  knockout  FAP  familial adenomatous polyposis  bHLH  basic helix-loop-helix  IBD  inflammatory bowel disease  CD  Crohn's disease  UC  ulcerative colitis  SNP  single nucleotide polymorphism  GSI  γ-secretase inhibitor  SMC  smooth muscle cells  ISEMF  intestinal subepithelial myofibroblasts
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