The Effect of GATA6 on miRNA in Lung Development
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE25874 | GEO | 2011/03/01
SECONDARY ACCESSION(S): PRJNA135803
REPOSITORIES: GEO
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Project description:Gata6 regulates lung epithelial stem cell development and airway regeneration. Here, the expression profile of microRNA was investigated when Gata6 was depleted during lung development. Analysis used total RNA from Sftpc-rtTA:tetO-cre lungs at E14.5 as control samples (WT) for comparison to the experimental samples of total RNA from Gata6flox/flox: Sftpc-rtTA: tetO-Cre mutant lungs at E14.5.
2011-03-01 | E-GEOD-25874 | biostudies-arrayexpress
Project description:Epithelial organs including the lung are known to possess regenerative abilities through activation of endogenous stem cell populations but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation in Gata6 null lung epithelium. This expansion of BASCs is the result of a dramatic increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the non-canonical Wnt receptor Fzd2 is down-regulated in Gata6 mutants and increased Fzd2 or decreased β-catenin expression rescues, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, we show that canonical Wnt signaling is activated in the niche containing BASCs and forced activation of Wnt signaling leads to a dramatic increase in BASC numbers. Moreover, Gata6 is required for proper lung epithelial regeneration and postnatal loss of Gata6 leads to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6 regulated Wnt signaling controls the balance between stem/progenitor expansion and epithelial differentiation required for both lung development and regeneration. Experiment Overall Design: 3 replicates of each condition-wild-type and GATA6 null tissue. 6 total samples.
2008-06-11 | E-GEOD-11165 | biostudies-arrayexpress
Project description:Epithelial organs including the lung are known to possess regenerative abilities through activation of endogenous stem cell populations but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation in Gata6 null lung epithelium. This expansion of BASCs is the result of a dramatic increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the non-canonical Wnt receptor Fzd2 is down-regulated in Gata6 mutants and increased Fzd2 or decreased β-catenin expression rescues, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, we show that canonical Wnt signaling is activated in the niche containing BASCs and forced activation of Wnt signaling leads to a dramatic increase in BASC numbers. Moreover, Gata6 is required for proper lung epithelial regeneration and postnatal loss of Gata6 leads to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6 regulated Wnt signaling controls the balance between stem/progenitor expansion and epithelial differentiation required for both lung development and regeneration. Keywords: gene targets in knockout mouse model
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Project description:Molecular programs that mediate normal cell differentiation are required for oncogenesis and tumor cell survival in certain cancers. How cell-lineage-restricted genes specifically influence metastasis is poorly defined. In lung cancers, we uncovered a transcriptional program that is preferentially associated with distal airway epithelial differentiation and lung adenocarcinoma (ADC) progression. This program is regulated in part by the lineage transcription factors GATA6 and HOPX. These factors can cooperatively limit the metastatic competence of ADC cells, by modulating overlapping alveolar differentiation and invasogenic target genes. Thus, GATA6 and HOPX are critical nodes in a lineage-selective pathway that directly links effectors of airway epithelial specification to the inhibition of metastasis in the lung ADC subtype.
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Project description:Lineage selective transcription factors (TFs) are important regulators of tumorigenesis, but their biological functions are often context dependent and their epigenetic mechanisms of action undefined. In this study, we uncover a conditional role for the endodermal and pulmonary specifying TF GATA6 during the initiation and progression of Kras mutant lung adenocarcinoma (LUAD). Inhibition of Gata6 in genetically engineered mouse models dampens the proliferation and increases the differentiation of LUAD tumors. These effects are influenced in part by the epithelial cell type that is targeted for transformation. In lung cancer cells derived from surfactant protein C expressing progenitors, we identify multiple genomic loci that are bound by GATA6. Moreover, suppression of Gata6 in these cells significantly alters chromatin accessibility, particularly at distal enhancer elements. Analogous to its paradoxical activity in the developing lungs, GATA6 expression fluctuates during different stages of LUAD progression and can control diverse lineage gene expression networks associated with cell proliferation, alveolar specification, BMP signaling, and epithelial plasticity. These findings demonstrate how GATA6 can broadly modulate the epigenome of lung tumor cells, which in turn may potentiate its divergent functions during cancer progression
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Project description:Lineage selective transcription factors (TFs) are important regulators of tumorigenesis, but their biological functions are often context dependent and their epigenetic mechanisms of action undefined. In this study, we uncover a conditional role for the endodermal and pulmonary specifying TF GATA6 during the initiation and progression of Kras mutant lung adenocarcinoma (LUAD). Inhibition of Gata6 in genetically engineered mouse models dampens the proliferation and increases the differentiation of LUAD tumors. These effects are influenced in part by the epithelial cell type that is targeted for transformation. In lung cancer cells derived from surfactant protein C expressing progenitors, we identify multiple genomic loci that are bound by GATA6. Moreover, suppression of Gata6 in these cells significantly alters chromatin accessibility, particularly at distal enhancer elements. Analogous to its paradoxical activity in the developing lungs, GATA6 expression fluctuates during different stages of LUAD progression and can control diverse lineage gene expression networks associated with cell proliferation, alveolar specification, BMP signaling, and epithelial plasticity. These findings demonstrate how GATA6 can broadly modulate the epigenome of lung tumor cells, which in turn may potentiate its divergent functions during cancer progression
2020-03-05 | GSE124603 | GEO
Project description:Lineage selective transcription factors (TFs) are important regulators of tumorigenesis, but their biological functions are often context dependent and their epigenetic mechanisms of action undefined. In this study, we uncover a conditional role for the endodermal and pulmonary specifying TF GATA6 during the initiation and progression of Kras mutant lung adenocarcinoma (LUAD). Inhibition of Gata6 in genetically engineered mouse models dampens the proliferation and increases the differentiation of LUAD tumors. These effects are influenced in part by the epithelial cell type that is targeted for transformation. In lung cancer cells derived from surfactant protein C expressing progenitors, we identify multiple genomic loci that are bound by GATA6. Moreover, suppression of Gata6 in these cells significantly alters chromatin accessibility, particularly at distal enhancer elements. Analogous to its paradoxical activity in the developing lungs, GATA6 expression fluctuates during different stages of LUAD progression and can control diverse lineage gene expression networks associated with cell proliferation, alveolar specification, BMP signaling, and epithelial plasticity. These findings demonstrate how GATA6 can broadly modulate the epigenome of lung tumor cells, which in turn may potentiate its divergent functions during cancer progression
2020-03-05 | GSE124602 | GEO
Project description:MicroRNA expression levels were assessed during the canalicular phase of normal fetal lung development at the critical time, when the distal airway epithelium proliferates and differentiates. Precise miRNA regulation is important for proper pulmonary organogenesis, supporting the delicate balance between expansion of progenitor cells and their terminal differentiation. Microarray analyses could indicate the potential involvement of miRNAs important for human pulmonary hypoplasia. Two replicates of pooled RNA from two 18-20 week old fetal lung samples
2016-02-05 | E-GEOD-76920 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE32600: Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (colony) GSE32602: Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (LCM_Four populations of cells) GSE32604: Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (stem cell clones NESC,TASC,DASC) Refer to individual Series
2011-11-01 | E-GEOD-32606 | biostudies-arrayexpress