Faculty Opinions recommendation of A constant pool of Lgr5+ intestinal stem cells is required for intestinal homeostasis.

2021 ◽  
Author(s):  
Malcolm Alison
Keyword(s):  
Stem Cells ◽  
Intestinal Stem Cells ◽  
Intestinal Homeostasis

scholarly journals Wnt/β-Catenin Is Essential for Intestinal Homeostasis and Maintenance of Intestinal Stem Cells

2007 ◽  
Vol 27 (21) ◽  
pp. 7551-7559 ◽  
Author(s):  
Tea Fevr ◽  
Sylvie Robine ◽  
Daniel Louvard ◽  
Joerg Huelsken
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Intestinal Epithelium ◽  
Transcriptional Profiling ◽  
Wnt Signaling Pathway ◽  
Intestinal Stem Cells ◽  
Intestinal Homeostasis ◽  
Adult Mice ◽  
Gene Ablation ◽  
Functional Preservation

ABSTRACT The Wnt signaling pathway is deregulated in over 90% of human colorectal cancers. β-Catenin, the central signal transducer of the Wnt pathway, can directly modulate gene expression by interacting with transcription factors of the TCF/LEF family. In the present study we investigate the role of Wnt signaling in the homeostasis of intestinal epithelium by using tissue-specific, inducible β-catenin gene ablation in adult mice. Block of Wnt/β-catenin signaling resulted in rapid loss of transient-amplifying cells and crypt structures. Importantly, intestinal stem cells were induced to terminally differentiate upon deletion of β-catenin, resulting in a complete block of intestinal homeostasis and fatal loss of intestinal function. Transcriptional profiling of mutant crypt mRNA isolated by laser capture microdissection confirmed those observations and allowed us to identify genes potentially responsible for the functional preservation of intestinal stem cells. Our data demonstrate an essential requirement of Wnt/β-catenin signaling for the maintenance of the intestinal epithelium in the adult organism. This challenges attempts to target aberrant Wnt signaling as a new therapeutic strategy to treat colorectal cancer.

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

PROTEOMICS ◽  
2020 ◽  
Vol 20 (5-6) ◽  
pp. 1800419 ◽  
Author(s):  
Peter Yuli Xing ◽  
Sven Pettersson ◽  
Parag Kundu
Keyword(s):  
Stem Cells ◽  
Intestinal Stem Cells ◽  
Microbial Metabolites ◽  
Intestinal Homeostasis

scholarly journals Stress responsive miR-31 is a major modulator of mouse intestinal stem cells during regeneration and tumorigenesis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yuhua Tian ◽  
Xianghui Ma ◽  
Cong Lv ◽  
Xiaole Sheng ◽  
Xiang Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Radiation Injury ◽  
Intestinal Stem Cells ◽  
Potential Therapeutic Target ◽  
Intestinal Homeostasis ◽  
Intestinal Tumorigenesis ◽  
Stat3 Signaling ◽  
Coordinate Control ◽  
Stat3 Signaling Pathway

Intestinal regeneration and tumorigenesis are believed to be driven by intestinal stem cells (ISCs). Elucidating mechanisms underlying ISC activation during regeneration and tumorigenesis can help uncover the underlying principles of intestinal homeostasis and disease including colorectal cancer. Here we show that miR-31 drives ISC proliferation, and protects ISCs against apoptosis, both during homeostasis and regeneration in response to ionizing radiation injury. Furthermore, miR-31 has oncogenic properties, promoting intestinal tumorigenesis. Mechanistically, miR-31 acts to balance input from Wnt, BMP, TGFβ signals to coordinate control of intestinal homeostasis, regeneration and tumorigenesis. We further find that miR-31 is regulated by the STAT3 signaling pathway in response to radiation injury. These findings identify miR-31 as a critical modulator of ISC biology, and a potential therapeutic target for a broad range of intestinal regenerative disorders and cancers.

Intestinal stem cells and intestinal homeostasis in health and in inflammation: A review

Surgery ◽  
2016 ◽  
Vol 159 (5) ◽  
pp. 1237-1248 ◽  
Author(s):  
Alexander L.A. Bloemendaal ◽  
Nicolas C. Buchs ◽  
Bruce D. George ◽  
Richard J. Guy
Keyword(s):  
Stem Cells ◽  
Intestinal Stem Cells ◽  
Intestinal Homeostasis

scholarly journals A constant pool of Lgr5+ intestinal stem cells is required for intestinal homeostasis

Cell Reports ◽  
2021 ◽  
Vol 34 (4) ◽  
pp. 108633
Author(s):  
Si Hui Tan ◽  
Phyllis Phuah ◽  
Liang Thing Tan ◽  
Swathi Yada ◽  
Jasmine Goh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Intestinal Stem Cells ◽  
Intestinal Homeostasis

scholarly journals Arid1a is essential for intestinal stem cells through Sox9 regulation

2019 ◽  
Vol 116 (5) ◽  
pp. 1704-1713 ◽  
Author(s):  
Yukiko Hiramatsu ◽  
Akihisa Fukuda ◽  
Satoshi Ogawa ◽  
Norihiro Goto ◽  
Kozo Ikuta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Functional Role ◽  
Molecular Mechanisms ◽  
Intestinal Epithelial Cells ◽  
Lineage Tracing ◽  
Intestinal Stem Cells ◽  
Intestinal Epithelial ◽  
Intestinal Homeostasis ◽  
Self Renewal

Inactivating mutations of Arid1a, a subunit of the Switch/sucrose nonfermentable chromatin remodeling complex, have been reported in multiple human cancers. Intestinal deletion of Arid1a has been reported to induce colorectal cancer in mice; however, its functional role in intestinal homeostasis remains unclear. We investigated the functional role of Arid1a in intestinal homeostasis in mice. We found that intestinal deletion of Arid1a results in loss of intestinal stem cells (ISCs), decreased Paneth and goblet cells, disorganized crypt-villous structures, and increased apoptosis in adult mice. Spheroids did not develop from intestinal epithelial cells deficient for Arid1a. Lineage-tracing experiments revealed that Arid1a deletion in Lgr5+ ISCs leads to impaired self-renewal of Lgr5+ ISCs but does not perturb intestinal homeostasis. The Wnt signaling pathway, including Wnt agonists, receptors, and target genes, was strikingly down-regulated in Arid1a-deficient intestines. We found that Arid1a directly binds to the Sox9 promoter to support its expression. Remarkably, overexpression of Sox9 in intestinal epithelial cells abrogated the above phenotypes, although Sox9 overexpression in intestinal epithelial cells did not restore the expression levels of Wnt agonist and receptor genes. Furthermore, Sox9 overexpression permitted development of spheroids from Arid1a-deficient intestinal epithelial cells. In addition, deletion of Arid1a concomitant with Sox9 overexpression in Lgr5+ ISCs restores self-renewal in Arid1a-deleted Lgr5+ ISCs. These results indicate that Arid1a is indispensable for the maintenance of ISCs and intestinal homeostasis in mice. Mechanistically, this is mainly mediated by Sox9. Our data provide insights into the molecular mechanisms underlying maintenance of ISCs and intestinal homeostasis.

scholarly journals Dietary Factors in the Control of Gut Homeostasis, Intestinal Stem Cells, and Colorectal Cancer

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2936 ◽  
Author(s):  
Federica Francescangeli ◽  
Maria Laura De Angelis ◽  
Ann Zeuner
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Low Income ◽  
Dietary Factors ◽  
Intestinal Stem Cells ◽  
Intestinal Homeostasis ◽  
Increased Risk ◽  
Incidence And Mortality

Colorectal cancer (CRC) is the third commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Global CRC burden is expected to increase by 60% in the next decade, with low-income countries experiencing an escalation of CRC incidence and mortality in parallel to the adoption of western lifestyles. CRC incidence is also sharply increasing in individuals younger than 50 years, often presenting at advanced stages and with aggressive features. Both genetic and environmental factors have been recognized as major contributors for the development of CRC, the latter including diet-related conditions such as chronic inflammation and obesity. In particular, a diet rich in fat and sugars (Western-style diet, WSD) has been shown to induce multiple pathophysiological changes in the intestine linked to an increased risk of CRC. In this scenario, dietary factors have been recently shown to play novel unexpected roles in the regulation of intestinal stem cells (ISCs) and of the gut microbiota, which represent the two main biological systems responsible for intestinal homeostasis. Furthermore, diet is increasingly recognized to play a key role in the neoplastic transformation of ISCs and in the metabolic regulation of colorectal cancer stem cells. This review illustrates novel discoveries on the role of dietary components in regulating intestinal homeostasis and colorectal tumorigenesis. Particular focus is dedicated to new areas of research with potential clinical relevance including the effect of food components on ISCs and cancer stem cells (CSCs), the existence of CRC-specific microbial signatures and the alterations of intestinal homeostasis potentially involved in early-onset CRC. New insights on the role of dietary factors in intestinal regulation will provide new tools not only for the prevention and early diagnosis of CRC but also for improving the effectiveness of current CRC therapies.

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