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Gene expression profile of colonic goblet cells (GCs) from SpdefKO_RedMUC298trTg and RedMUC298trTg mice

ABSTRACT: Spdef is a transcription factor involved in differentiation of goblet cells. Goblet cells from RedMUC298trTg and Spdef -/-RedMUC298trTg were sorted to analyse the differential gene expression in the absence of Spdef.

ORGANISM(S): Mus musculus

PROVIDER: GSE158186 | GEO | 2021/04/16

REPOSITORIES: GEO

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The Ets domain transcription factor Spdef drives maturation of Goblet and Paneth cells in the intestinal epithelium

Project description:BACKGROUND & AIMS: Stems cells within the intestinal epithelium generate daughter cells which undergo lineage commitment and maturation through the concerted action of the Wnt and Notch signalling cascades. Both pathways, in turn, regulate transcription factor networks which further define differentiation towards either enterocytes or one of three secretory cell lineages (Paneth, goblet or enteroendocrine cells). In this manuscript, we identified the Ets domain transcription factor, Spdef, as a novel lineage maker of goblet and Paneth cells. METHODS: To address the function of Spdef in vivo, we inactivated the Spdef gene and analysed the intestinal phenotype using a range of histological techniques and DNA microarray profiling. RESULTS: In accordance with the expression data we found that loss of Spdef severely impaired the maturation of goblet and Paneth cells and conversely lead to an accumulation of immature secretory progenitors. Moreover, we provide evidence suggesting that Spdef positively and negatively regulates a specific subset of goblet and Paneth cell genes including Cryptdins, Mmp7, Ang4, Kallikreins, and Muc2. CONCLUSION: We propose a model whereby Spdef acts downstream of Math1 to promote terminal differentiation of a secretory progenitor pool towards Paneth and goblet cells. Keywords: expression profiling

2010-02-10 | GSE14892 | GEO

Expression data from Spdef +/+ and Spdef -/- mice

Project description:Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef -/- mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef -/- mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef -/- mice identified 43 signficantly upregulated genes and 110 signficantly downregulated genes in the conjunctival epithelium of Spdef -/- mice compared to that of Spdef +/+ control mice (3 fold change, p<0.01). Downregulated genes of particular interested included goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Upregulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and pro-inflammatory genes (Il1-Î±, Il-1Î², Tnf-Î±), all of which are upregulated in dry eye. Interestingly, four Wnt pathway genes were downregulated. Conjunctival epithelium of Spdef +/+ and Spdef -/- mice was collected by laser capture microdissection for RNA extraction and hybridization on Affymetrix microarrays to determine if gene expression patterns in the conjunctival epithelium of Spdef -/- mice is altered compared to that of Spdef +/+ mice.

2013-02-08 | E-GEOD-44101 | biostudies-arrayexpress

Gene expression profile of colonic goblet cells (GCs) from SpdefKO_RedMUC298trTg and RedMUC298trTg mice

Project description:Gene expression profile of colonic goblet cells (GCs) from SpdefKO_RedMUC298trTg and RedMUC298trTg mice

| PRJNA664463 | ENA

Cigarette Smoke Activates NOTCH3 to Promote Goblet Cell Differentiation in Human Airway Epithelial Cells

Project description:Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death in the United States and is caused primarily by cigarette smoking. Increased numbers of mucus-producing secretory (“goblet”) cells defined as goblet cell metaplasia or hyperplasia (GCMH), contributes significantly to COPD pathophysiology. The objective of this study was to determine whether NOTCH signaling regulates goblet cell differentiation in response to cigarette smoke. To this end, primary human bronchial epithelial cells (HBECs) from nonsmokers and COPD smokers were differentiated in vitro on air-liquid interface and exposed to cigarette smoke extract (CSE) for 7 days. NOTCH signaling activity was modulated using (1) the NOTCH/γ-secretase inhibitor Dibenzazepine (DBZ), (2) lentiviral over-expression of the NOTCH3-intracellular domain (NICD3) or (3) NOTCH3-specific siRNA. Cell differentiation and response to CSE were evaluated by qPCR, Western blotting, immunostaining and RNA-Seq. Our data demonstrate that CSE exposure of nonsmoker airway epithelium induced goblet cell differentiation characteristic of GCMH. Treatment with DBZ suppressed CSE-dependent induction of goblet cell differentiation. Furthermore, CSE induced NOTCH3 activation, as revealed by increased NOTCH3 nuclear localization and elevated NICD3 protein levels. Over-expression of NICD3 increased expression of the goblet cell associated genes SPDEF and MUC5AC, whereas NOTCH3 knockdown suppressed CSE-mediated induction of SPDEF and MUC5AC. Finally, CSE exposure of COPD airway epithelium induced goblet cell differentiation in a NOTCH3-dependent manner. These results identify NOTCH3 activation as one of the important mechanisms by which cigarette smoke induces goblet cell differentiation, thus providing a potential strategy to control GCMH-related pathologies in smokers and patients with COPD.

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Transcription profiling of mouse colonic goblet cells deficient in Atg5

Project description:Purpose of this experiment was to gain insight into the transcriptional changes resulting from Atg5 deficiency in colonic goblet cells.

2010-09-30 | E-TABM-815 | biostudies-arrayexpress

Expression data from Spdef +/+ and Spdef -/- mice

Project description:Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef -/- mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef -/- mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef -/- mice identified 43 signficantly upregulated genes and 110 signficantly downregulated genes in the conjunctival epithelium of Spdef -/- mice compared to that of Spdef +/+ control mice (3 fold change, p<0.01). Downregulated genes of particular interested included goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Upregulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and pro-inflammatory genes (Il1-α, Il-1β, Tnf-α), all of which are upregulated in dry eye. Interestingly, four Wnt pathway genes were downregulated.

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Project description:Goblet cells together other cell types make up the intestinal epithelium and are responsible for mucus production. The goal of this project is to fully characterize the gene expression profile of the GCs in the colon and small intestine.

2021-04-16 | GSE144363 | GEO

Gene expression profile at single cell level of goblet cells (GCs) from the distal colon (DC) and the 8th portion of the small intestine (Si8)

Project description:Goblet cells are considered as a homogeneous population in the intestinal epithelium. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of GCs in the intestine.

2021-04-16 | GSE144364 | GEO

Gene expression in small intestinal and colonic goblet cells from C57Bl/6 mice

Project description:Microarray analysis of goblet cells isolated from the small intestine or colon was completed to compare the cells between the two parts of the intestine.

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