GATA Factors Regulate Proliferation, Differentiation, and Gene Expression in Small Intestine of Mature Mice

Beuling, Eva; Baffour-Awuah, Nana Yaa; Stapleton, Kelly A.; Aronson, Boaz E.; Noah, Taeko K.; Shroyer, Noah F.; Duncan, Stephen A.; Fleet, James C.; Krasinski, Stephen D.

doi:10.1053/j.gastro.2011.01.033

Cited by 97 publications

(155 citation statements)

References 43 publications

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“…Since GATA6 is highly expressed in the crypt compartment in the intestine 19 , it may also play an essential role in the regulation of Lgr5 expression in intestinal stem cells. Consistent with this notion, it has recently been reported that conditional deletion of GATA6 in intestinal epithelium results in decreased proliferation of crypt progenitor cells and abnormal differentiation of secretary cells 26 .…”

Section: Discussionsupporting

confidence: 54%

“…GATA6 is a zinc finger transcription factor that is required for the proliferation, development and specific gene regulation of the gastrointestinal tract and other tissues [24][25][26] . GATA6 has also been reported to be involved in colorectal tumour invasion and in the conversion of Barrett metaplasia to adenocarcinoma 27,28 .…”

Section: Gata6 Upregulates Lgr5 Expression In Colorectal Cancer Cellsmentioning

confidence: 99%

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The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis

et al. 2014

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Aberrant activation of Wnt signalling results in colorectal tumours. Lgr5 is specifically expressed in stem cells of the intestine and has an essential role in maintaining tissue homeostasis. Lgr5-positive stem cells are responsible for the intestinal adenoma initiated by mutations in adenomatous polyposis coli. Furthermore, Lgr5 interacts with R-spondins and thereby activates Wnt signalling. However, the function of Lgr5 in colorectal tumourigenesis is unclear. Here we show that LGR5 is required for the tumourigenicity of colorectal cancer cells. We show that the transcription factor GATA6 directly enhances the expression of LGR5. We further demonstrate that GATA6 is upregulated in colorectal cancer cells due to the downregulation of miR-363, which directly targets GATA6. Moreover, we show that overexpression of miR-363 suppresses the tumourigenicity of colorectal cancer cells. These results suggest that the miR-363-GATA6-LGR5 pathway is critical for colorectal tumourigenesis and would be a promising target for the treatment of colorectal cancer.

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Section: Discussionsupporting

confidence: 54%

Section: Gata6 Upregulates Lgr5 Expression In Colorectal Cancer Cellsmentioning

confidence: 99%

The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis

et al. 2014

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“…4c,e), or with proximal vs . distal intestinal identity (known: Gata4 , Nr1h4 24 and novel: Creb3l3, Jund, Osr2, Nr1i3 ; Extended Data Fig. 4d).…”

Section: Resultsmentioning

confidence: 99%

A single-cell survey of the small intestinal epithelium

Haber

Biton

Rogel

et al. 2017

Nature

1,416

115

1,694

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Intestinal epithelial cells (IECs) absorb nutrients, respond to microbes, provide barrier function and help coordinate immune responses. We profiled 53,193 individual epithelial cells from mouse small intestine and organoids, and characterized novel subtypes and their gene signatures. We showed unexpected diversity of hormone-secreting enteroendocrine cells and constructed their novel taxonomy. We distinguished between two tuft cell subtypes, one of which expresses the epithelial cytokine TSLP and CD45 (Ptprc), the pan-immune marker not previously associated with non-hematopoietic cells. We also characterized how cell-intrinsic states and cell proportions respond to bacterial and helminth infections. Salmonella infection caused an increase in Paneth cells and enterocytes abundance, and broad activation of an antimicrobial program. In contrast, Heligmosomoides polygyrus caused an expansion of goblet and tuft cell populations. Our survey highlights new markers and programs, associates sensory molecules to cell types, and uncovers principles of gut homeostasis and response to pathogens.

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“…It has been shown that GATA4 or GATA6 is necessary for secretory progenitors to commit to a neuroendocrine lineage. [167][168][169] Immunohistochemical analysis of mouse small intestine revealed that GATA4 is only expressed in villus enterocytes. GATA5 was not detected in enterocytes, but it was detected in other lineages.…”

Section: Cell Differentiation and Intestinal Adaptationmentioning

confidence: 99%

Isolated ileal interposition in enteroendocrine L cells differentiation

Cardia¹,

Azevedo²,

Azevedo³

et al. 2011

Nature Precedings

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INTRODUCTION:Due to the progressive nature of type 2 diabetes, its complexity and drug treatment perpetuity, there is currently a search for surgical procedures that can promote euglycemia also in non-obese patients. Diabetic patients glycemic control can be achieved by increasing the blood concentration of GLP-1, a hormone produced by L cells that are more densely concentrated in the terminal ileum. Early and extended improvement of diabetes in patients submitted to bariatric surgeries awakened the necessity of investigating the isolated ileal interposition as surgical alternative for the treatment of diabetes. The interposition of this ileal segment to a more anterior region (proximal jejunum) can promote a greater stimulation of the L cells by poorly digested food, increasing the production of GLP-1 and reflecting on glycemic control. However, in order to consolidate the ileal interposition as a surgical treatment of diabetes it is necessary that the interposed ileum keep the same differentiation rate into L cells for a long period to justify the intervention. AIMS:To investigate the isolated ileal interposition influence on the differentiation of intestinal precursor cells into enteroendocrine L cells over time. METHODS:Twelve 12-week-old male Wistar rats (Rattus norvegicus albinus) of the WAB strain (heterogeneous) will be used. All animals will receive a high-calorie, high-fat diet for 16 weeks or more until they develop glucose dysmetabolism confirmed by glycemic test. They will be divided into two groups of 10 animals each: the isolated ileal interposition group (GI) and the control group (GC), comprising animals that will not be submitted to any surgical intervention.Blood samples will be collected under anesthesia at the weeks 12, 26, 36 and 44 for the determination of serum levels of glucose, insulin, GLP-1, glucagon, C-peptide and glycosilated hemoglobin. The insulin tolerance test will be performed and insulin resistance will be calculated. For the comparative analysis of the ileal precursor cells differentiation into enteroendocrine cells among the two groups, the following intestinal fragments will be collected after euthanasia: interposed ileum and remaining ileum from GI, jejunum and ileum from GC. These fragments will be analyzed by imunofluorescence and also by Real Time PCR using PCR Arrays for target genes including the main ones related to stem cell, stem cell singnalling, diabetes, Wnt and Notch signaling pathways and other genes and pathways involved in the differentiation of intestinal precursor cells into enteroendocrine cells, especially GLP-1-producing L cells that play important role in euglycemia.

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GATA Factors Regulate Proliferation, Differentiation, and Gene Expression in Small Intestine of Mature Mice

Cited by 97 publications

References 43 publications

The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis

The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis

A single-cell survey of the small intestinal epithelium

Isolated ileal interposition in enteroendocrine L cells differentiation

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