Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hmga2 is required for canonical WNT signaling during lung development

ABSTRACT: The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. Here we deciphered the role of the high mobility group AT-hook protein 2 (HMGA2) during lung development by analyzing the lung of Hmga2 deficient mice (Hmga2-/-).We found that Hmga2 is expressed in the mouse embryonic lung at the distal airways. Analysis of Hmga2-/- mice showed that Hmga2 is required for proper cell proliferation and distal epithelium differentiation during embryonic lung development. Hmga2 knockout (KO) led to enhanced canonical WNT signaling due to an increased expression of secreted WNT glycoproteins Wnt2b, Wnt7b and Wnt11 as well as a reduction of the WNT signaling antagonizing proteins GATA6 (GATA binding protein 6) and FZD2 (frizzled homolog 2). Comparison of Hmga2-/- with Hmga2+/+ mice by Affymetrix microarray-based expression analysis of embryonic lung revealed an increased expression of genes whose products participate in cell cycle and canonical Wnt signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE55340 | GEO | 2014/03/07

SECONDARY ACCESSION(S): PRJNA239356

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hmga2 is required for canonical WNT signaling during lung development

Project description:The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. Here we deciphered the role of the high mobility group AT-hook protein 2 (HMGA2) during lung development by analyzing the lung of Hmga2 deficient mice (Hmga2-/-).We found that Hmga2 is expressed in the mouse embryonic lung at the distal airways. Analysis of Hmga2-/- mice showed that Hmga2 is required for proper cell proliferation and distal epithelium differentiation during embryonic lung development. Hmga2 knockout (KO) led to enhanced canonical WNT signaling due to an increased expression of secreted WNT glycoproteins Wnt2b, Wnt7b and Wnt11 as well as a reduction of the WNT signaling antagonizing proteins GATA6 (GATA binding protein 6) and FZD2 (frizzled homolog 2). Comparison of Hmga2-/- with Hmga2+/+ mice by Affymetrix microarray-based expression analysis of embryonic lung revealed an increased expression of genes whose products participate in cell cycle and canonical Wnt signaling. Affymetrix microarray transcriptome analysis of Hmga2-/- and Hmga2+/+ embryonic lung (E18.5) was performed and analyzed

2014-03-07 | E-GEOD-55340 | biostudies-arrayexpress

Role of Fzd2 in lung epithelium development

2014-07-29 | GSE49370 | GEO

Role of Fzd2 in lung epithelium development

Project description:Fzd2 is a Wnt receptor expressed in the embryonic lung. We made a conditional knockout of Fzd2 to specifically address the role of signaling through Fzd2 in lung epithelial development. To explore the genes that are regulated by signaling through the Fzd2 receptor in the lung epithelium, we performed microarray analysis of Shhcre control and Fzd2CKO lungs at E12.5

2014-07-29 | E-GEOD-49370 | biostudies-arrayexpress

Transcription profiling ofmouse wild type and GATA6 null lung

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 Î²-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

Genes regulated by GATA6 in the lung

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

2008-04-15 | GSE11165 | GEO

High Mobility Group protein mediated transcription requires DNA damage marker Î³-H2AX

Project description:The eukaryotic genome is organized into chromatin, which constitutes the physiological template for DNA-dependent processes including replication, recombination, repair and transcription. Chromatin mediated transcription regulation involves histone modifications, chromatin remodeling and DNA methylation. However, the precise biological function of non-histone chromatin-associated proteins is still unclear. The high mobility group proteins are the most abundant non-histone chromatin-associated proteins. Here we combined proteomic, ChIP-seq and transcriptome data to decipher the mechanism of transcriptional regulation mediated by the high mobility group AT-hook protein 2 (HMGA2). We showed that HMGA2-induced transcription requires H2AX phosphorylation at S139 (H2AXS139ph; Î³-H2AX), mediated by the kinase ataxia telangiectasia mutated (ATM). Furthermore, we demonstrated the relevance of this mechanism within the biological context of TGFB1-signaling. Our results link H2AXS139ph, a marker for DNA damage, to transcription, which is a new function for this histone modification. The interplay between HMGA2, ATM and H2AX is a novel mechanism of transcription initiation. Chip-seq data of HMGA2, H2AXS139ph and ATM obtained from Mouse embryonic Fibroblast cells in wt and Ko of Hmga2

2015-11-04 | E-GEOD-63861 | biostudies-arrayexpress

Mus musculus

Project description:Hmga2 is required for canonical WNT signaling during lung development

| PRJNA239356 | ENA

Pan-cancer analysis of the developmental pathways reveals non-canonical wnt signaling as a driver of mesenchymal-type tumors

Project description:The processes of angiogenesis, cell proliferation, invasion, and migration, and the signaling pathways that drive these events, are activated in both cancer and during embryonic development. Here, we systematically assessed how the activity of major developmental signaling pathways, represented by the expression of genes encoding components of the pathways, correlated with patient survival in ~8000 patients across 17 cancer types. We also compared the expressed genes enriched in developmental pathways with those associated with epithelial-mesenchymal transition (EMT) both in a cancer cohort and in mice during embryonic development. We found that EMT and gene expression profiles consistent with high activity of several developmental pathways, including the TGFβ, Notch, and non-canonical Wnt pathways, significantly correlated with poor patient survival in multiple cancer types. We investigated individual components of these pathways and found that expression of the gene encoding the non-canonical Wnt receptor, frizzled 2 (FZD2), is highly correlated with both poor patient survival and gene expression indicating EMT in the tumors. Pathway analyses revealed that FZD2-regulated gene sets from the TCGA data or FZD2-regulated genes involved in mouse organogenesis or FZD2-regulated genes in cancer cells in culture converged in EMT-associated biological processes, suggesting that FZD2 is a key driver of mesenchymal-like cell state and thus a contributor to cancer progression and metastasis.

2020-08-01 | GSE138380 | GEO

Gene expression profile of embryonic retinas expressing c-hairy1, Delta-1, or Wnt2b

Project description:Expression profile of embryonic retinas expressing exogenous c-hairy1, Delta-1, or Wnt2b. These genes inhibits neuronal differentiation, and the results provide insight into the mechanism that keeps retinal progenitor cells undifferentiated. In the vertebrate retina, stem cell-like progenitor cells are maintained in a distinct region, called the ciliary marginal zone (CMZ). Canonical Wnt signaling regulates the maintenance of the progenitor cells in the CMZ. However, its downstream molecular mechanisms have remained largely unclear. Here, we show that c-hairy1, an established Notch signaling effector, mediates the Wnt-dependent maintenance of CMZ progenitor cells in chickens. Interestingly, unlike other developmental contexts where Hes gene expression is regulated by Notch signaling, the c-hairy1 expression in the CMZ is regulated by Wnt signaling. c-hairy1 is necessary and sufficient for the expression of a set of molecular markers characteristic of the CMZ, and Wnt2b fails to induce CMZ markers when c-hairy1 activity is inhibited. Furthermore, microarray analysis identifies multiple Wnt-responsive transcription factors that activate c-hairy1 expression. We thus propose that c-hairy1 functions as a node downstre am of Wnt signaling to maintain progenitor cells in the CMZ. Total RNA was purified from E6.5 retinas transfected either with c-hairy1, Wnt2b, Delta, or mock-expressing RCAS plasmid using Trizol reagent (Invitrogen). Microarray analysis using Gene Chip Chicken Genome Array (Affymetrix) was performed according to the manufacturer’s protocols. Data were analyzed using GCOS (Affymetrix) and dChip (Li and Wong, 2001). GCOS and dChip produced similar results. The data submitted is from GCOS. To explore candidates for new Wnt target genes, genes with higher expression in Wnt2b-expressing retina than control or Delta1-expressing retinas were selected for further analysis.

2009-03-27 | E-GEOD-15382 | biostudies-arrayexpress

Gene expression profile of embryonic retinas expressing c-hairy1, Delta-1, or Wnt2b

2009-03-27 | GSE15382 | GEO