The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands

Lavery, Danielle L.; Nicholson, Anna M.; Poulsom, Richard; Jeffery, Rosemary; Hussain, Alia; Jankowski, Janusz; Zeki, Sebastian; Barr, Hugh; Harrison, Rebecca; Going, James J.; Kadirkamanathan, Sritharan; Davis, Peter E.; Underwood, Tim; Novelli, Marco; Rodriguez‐Justo, Manuel; Shepherd, Neil A.; Jansen, Marnix; Wright, Nicholas; McDonald, Stuart

doi:10.1136/gutjnl-2013-306508

Cited by 68 publications

(75 citation statements)

References 30 publications

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“…In contrast, in adjacent corpus glands, no Lgr5-GFP positive cells were present, and the proliferative zone was located closer to the lumen. 43 Thus, the proliferative organization of the first gland appears to mimic the structure in antral glands.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, Barrett's esophagus expresses a similar pattern of gene expression as that found in antral gastric glands. 43 The position of the first gland and the existence of Lgr5-postive progenitor cells as well as numerous tuft cells all support a possible role for the first gland in generating the Barrett's epithelium. It is also notable that MUC4 and EpCAM are strongly expressed in Barrett's epithelium.…”

Section: Discussionmentioning

confidence: 99%

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Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric Corpus

O’Neil

Petersen

Choi

et al. 2016

J Histochem Cytochem.

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SummaryThe glandular stomach has two major zones: the acid secreting corpus and the gastrin cell-containing antrum. Nevertheless, a single gland lies at the transition between the forestomach and corpus in the mouse stomach. We have sought to define the lineages that make up this gland unit at the squamocolumnar junction. The first gland in mice showed a notable absence of characteristic corpus lineages, including parietal cells and chief cells. In contrast, the gland showed strong staining of Griffonia simplicifolia-II (GSII)-lectin-positive mucous cells at the bases of glands, which were also positive for CD44 variant 9 and Clusterin. Prominent numbers of doublecortin-like kinase 1 (DCLK1) positive tuft cells were present in the first gland. The first gland contained Lgr5-expressing putative progenitor cells, and a large proportion of the cells were positive for Sox2. The cells of the first gland stained strongly for MUC4 and EpCAM, but both were absent in the normal corpus mucosa. The present studies indicate that the first gland in the corpus represents a unique anatomic entity. The presence of a concentration of progenitor cells and sensory tuft cells in this gland suggests that it may represent a source of reserve reparative cells for adapting to severe mucosal damage. (J Histochem Cytochem 65:47-58, 2017)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric Corpus

O’Neil

Petersen

Choi

et al. 2016

J Histochem Cytochem.

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“…This argument is further supported by the lack of miR-215 expression in the cancer stem cell-enriched fractions of differentiated cell lines. Significantly, aberrant miR-215 expression is also coincident with CDX1 activation in Barrett's esophagus (13,39), suggesting that this axis is important in intestinal metaplasia (40).…”

Section: Discussionmentioning

confidence: 99%

The CDX1–microRNA-215 axis regulates colorectal cancer stem cell differentiation

Jones

Hara²,

Francis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The transcription factor caudal-type homeobox 1 (CDX1) is a key regulator of differentiation in the normal colon and in colorectal cancer (CRC). CDX1 activates the expression of enterocyte genes, but it is not clear how the concomitant silencing of stem cell genes is achieved. MicroRNAs (miRNAs) are important mediators of gene repression and have been implicated in tumor suppression and carcinogenesis, but the roles of miRNAs in differentiation, particularly in CRC, remain poorly understood. Here, we identified microRNA-215 (miR-215) as a direct transcriptional target of CDX1 by using highthroughput small RNA sequencing to profile miRNA expression in two pairs of CRC cell lines: CDX1-low HCT116 and HCT116 with stable CDX1 overexpression, and CDX1-high LS174T and LS174T with stable CDX1 knockdown. Validation of candidate miRNAs identified by RNA-seq in a larger cell-line panel revealed miR-215 to be most significantly correlated with CDX1 expression. Quantitative ChIP-PCR and promoter luciferase assays confirmed that CDX1 directly activates miR-215 transcription. miR-215 expression is depleted in FACS-enriched cancer stem cells compared with unsorted samples. Overexpression of miR-215 in poorly differentiated cell lines causes a decrease in clonogenicity, whereas miR-215 knockdown increases clonogenicity and impairs differentiation in CDX1-high cell lines. We identified the genome-wide targets of miR-215 and found that miR-215 mediates the repression of cell cycle and stemness genes downstream of CDX1. In particular, the miR-215 target gene BMI1 has been shown to promote stemness and self-renewal and to vary inversely with CDX1. Our work situates miR-215 as a link between CDX1 expression and BMI1 repression that governs differentiation in CRC.T he caudal-type homeobox 1 (CDX1) transcription factor controls enterocyte differentiation in the colon, where its expression is excluded from the crypt-base stem cell compartment. CDX1 is also central to the capacity of a colorectal cancer (CRC) cell line to differentiate, and it is a negative marker of CRC stem cells (1-3). In 19% of CRC cell lines assayed in a large study, CDX1 expression was completely lost due to promoter methylation and was down-regulated in a further 13% as a result of hemimethylation of the promoter (4). Comparison of CDX1 expression in colorectal adenocarcinoma versus matched normal tissue showed downregulation of CDX1 in 73% of tumors, which was also attributable to promoter methylation (5). Expression of CDX1 also correlates inversely with that of the polycomb complex protein BMI1, which is necessary for the maintenance of quiescent injury-inducible stem cells in the normal crypt and is expressed in cancer stem cells (2, 6-8). The mechanism underlying this inverse correlation has not yet been elucidated.In addition to these correlative data, CDX1 has also been shown to promote directly the expression of structural proteins important for epithelial differentiation including cytokeratin 20 (KRT20) (1), villin (VIL) (9), and FABP1 (10). Introduction...

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“…This corresponds to a change of the epithelium characteristics towards a different type of epithelium. For instance, the esophagus epithelium shows features of intestinal epithelium and pyloric-type gastric glands in patients with Barrett's esophagus syndrome or following Helicobacter pylori infection [104,137,138]. Epithelial metaplasia is the result of homeotic transformations (i.e., the aberrant differentiation of one region into another, implying misregulation of homeotic genes) [139].…”

Section: Mesenchymal-epithelial Interactions In Stem Cell Regeneratiomentioning

confidence: 99%

Mesenchymal–epithelial interactions during digestive tract development and epithelial stem cell regeneration

Guen

Marchal

Faure

et al. 2015

Cell. Mol. Life Sci.

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The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior-posterior and dorso-ventral axes of asymmetry. It is derived from all three germ layers and their cross-talk is important for the regulated development of fetal and adult gastrointestinal structures and organs. Signals from the adjacent mesoderm are essential for the morphogenesis of the overlying epithelium. These mesenchymal-epithelial interactions govern the development and regionalization of the different gastrointestinal epithelia and involve most of the key morphogens and signaling pathways, such as the Hedgehog, BMPs, Notch, WNT, HOX, SOX and FOXF cascades. Moreover, the mechanisms underlying mesenchyme differentiation into smooth muscle cells influence the regionalization of the gastrointestinal epithelium through interactions with the enteric nervous system. In the neonatal and adult gastrointestinal tract, mesenchymal-epithelial interactions are essential for the maintenance of the epithelial regionalization and digestive epithelial homeostasis. Disruption of these interactions is also associated with bowel dysfunction potentially leading to epithelial tumor development. In this review, we will discuss various aspects of the mesenchymal-epithelial interactions observed during digestive epithelium development and differentiation and also during epithelial stem cell regeneration.

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The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands

Cited by 68 publications

References 30 publications

Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric Corpus

Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric Corpus

The CDX1–microRNA-215 axis regulates colorectal cancer stem cell differentiation

Mesenchymal–epithelial interactions during digestive tract development and epithelial stem cell regeneration

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