Comparison of Zmiz1-induced keratoancanthoma and normal skin
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE39360 | GEO | 2012/10/01
SECONDARY ACCESSION(S): PRJNA170737
REPOSITORIES: GEO
Similar Datasets
Project description:Transgenic mice expressing a truncated form of Zmiz1 in the skin develop spontaneous keratoacanthomas. In this experiment, a Cre-inducible transgene expressing a truncated form of Zmiz1 was introduced into mice. Activation of the transgene in these mice was achieved by breeding to K14-Cre transgenic animals. Double transgenic mice formed spontaenous keratoacanthomas with short latency. In this experiment, we generated gene expression profiles for five Zmiz1-induced keratoacanthomas and six normal skin samples.
2012-10-01 | E-GEOD-39360 | biostudies-arrayexpress
Project description:The homeostasis of both cornea and hair follicles depends on a constant supply of progeny cells produced by populations of keratin (K) 14-expressing stem cells localized in specific niches. To investigate the potential role of Co-factors of LIM domains (Clims) in such tissues, we generated transgenic mice expressing a dominant-negative Clim molecule (DN-Clim) under the control of the K14 promoter. As expected, the K14 promoter directed high level expression of the transgene to the basal cells of cornea and epidermis, as well as the outer root sheath of hair follicles. In corneal epithelium, the transgene expression causes decreased expression of adhesion molecule BP180 and defective hemidesmosomes, leading to detachment of corneal epithelium from the underlying stroma, which in turn causes blisters, wounds and an inflammatory response. After a period of epithelial thinning, the corneal epithelium undergoes differentiation to an epidermis-like structure. The K14-DN-Clim mice also develop progressive hair loss due to dysfunctional hair follicles that fail to generate hair shafts. The number of hair follicle stem cells is decreased by at least 50% in K14-DN-Clim mice, indicating that Clims are required for hair follicle stem cell maintenance. We hypothesize that Clim2 is an essential co-factor for the LIM homeodomain factor Lhx2, which was previously shown to play a role in hair follicle stem cell maintenance. Together, these data indicate that Clim proteins play important roles in the homeostasis of corneal epithelium and hair follicles. Keywords: Comparison of wild-type and transgenic skin tissue
2007-06-23 | GSE8227 | GEO
Project description:The most recurrently mutated oncogene in T-cell acute lymphoblastic leukemia (T-ALL) is NOTCH1. The core Notch complex consists of an ICN protein, a Maml cofactor, and the DNA binding factor Rbpj. The known direct cofactors of Notch appear to act nonselectively, homogeneously driving Notch gene expression functions. It is unclear whether there are direct cofactors of Notch that act selectively and heterogeneously regulate ICN. We discovered that Zmiz1, a Protein Inhibitor of Activated STAT (PIAS)-like coactivator, directly bound ICN1. ChIP-Seq showed that Zmiz1 selectively co-bound only a subset of Notch-regulated enhancers. This led to hypothesize that Zmiz1 regulates only a subset of Notch1 target genes. To investigate this, we performed RNA-Seq on four 8946 cell linesin which L1601P (activated Notch1) or Zmiz1 were expressed alone or in combination. Zmiz1 induced ~10% of Notch target genes. The Notch target gene that was most strongly induced by Zmiz1 was Myc. Our data suggest that Zmiz1 selectively amplifies a subset of Notch target genes with strong amplification of Myc. RNA-Seq in a murine T-ALL cell line
2015-10-28 | E-GEOD-66145 | biostudies-arrayexpress
Project description:The most recurrently mutated oncogene in T-cell acute lymphoblastic leukemia (T-ALL) is NOTCH1. The core Notch complex consists of an ICN protein, a Maml cofactor, and the DNA binding factor Rbpj. The known direct cofactors of Notch appear to act nonselectively, homogeneously driving Notch gene expression functions. It is unclear whether there are direct cofactors of Notch that act selectively and heterogeneously regulate ICN. We discovered that Zmiz1, a Protein Inhibitor of Activated STAT (PIAS)-like coactivator, directly bound ICN1. In order to determine whether this interaction occured at chromatin, we performed ChIP-Seq. We identified significant overlap between ICN1, Rbpj, and Zmiz1 peaks. 75% of overlapping ICN1/Rbpj peaks overlapped with Zmiz1 (HA) peaks (273 peaks). The size of Zmiz1 (HA) peaks had moderate correlation with the size of Rbpj and ICN1 peaks. Like Rbpj and ICN1 peaks, Zmiz1 (HA) peaks were associated with activating H3K27ac, H3K4me1, and H3K4me3 chromatin marks and were devoid of repressive H3K27me3 marks. These data suggest that Zmiz1 is a selective Notch regulator. It co-binds only a subset of ICN1 and Rbpj-regulated sites. Zmiz1, ICN1, Rbpj, histone mehylation ChIP-Seq in murine T-ALL cell line
2015-10-28 | E-GEOD-66146 | biostudies-arrayexpress
Project description:The homeostasis of both cornea and hair follicles depends on a constant supply of progeny cells produced by populations of keratin (K) 14-expressing stem cells localized in specific niches. To investigate the potential role of Co-factors of LIM domains (Clims) in such tissues, we generated transgenic mice expressing a dominant-negative Clim molecule (DN-Clim) under the control of the K14 promoter. As expected, the K14 promoter directed high level expression of the transgene to the basal cells of cornea and epidermis, as well as the outer root sheath of hair follicles. In corneal epithelium, the transgene expression causes decreased expression of adhesion molecule BP180 and defective hemidesmosomes, leading to detachment of corneal epithelium from the underlying stroma, which in turn causes blisters, wounds and an inflammatory response. After a period of epithelial thinning, the corneal epithelium undergoes differentiation to an epidermis-like structure. The K14-DN-Clim mice also develop progressive hair loss due to dysfunctional hair follicles that fail to generate hair shafts. The number of hair follicle stem cells is decreased by at least 50% in K14-DN-Clim mice, indicating that Clims are required for hair follicle stem cell maintenance. We hypothesize that Clim2 is an essential co-factor for the LIM homeodomain factor Lhx2, which was previously shown to play a role in hair follicle stem cell maintenance. Together, these data indicate that Clim proteins play important roles in the homeostasis of corneal epithelium and hair follicles. Experiment Overall Design: We profiled mRNA expression in mouse back skin from 3 time points, representing the initial hair follicle morphogenesis (P6 and P14) and the first telogen (P23); hair growth is synchronized during these time points. For each time point, RNA was isolated and analyzed from 3 to 5 transgenic mice and same number of wild-type littermates.
2008-06-16 | E-GEOD-8227 | biostudies-arrayexpress
Project description:Multiple transgenic mice expressing Cre. Raw sequence reads
| PRJNA343439 | ENA
Project description:We employed isobaric labeled peptides to do bottom-up proteomics to quantify both non-enriched total peptides and enriched phospho-peptides obtained from hearts of control mice expressing wild-type cardiac troponin I and transgenic mice expressing the truncated N-terminal cardiac troponin I.
2021-03-15 | MSV000087049 | MassIVE
Project description:In human basal-like breast cancer, mutations and deletions in TP53 and BRCA1 are frequent oncogenic events. Thus, we interbred mice expressing the CRE-recombinase with mice harboring loxP sites at TP53 and BRCA1 (K14-Cre; p53F/F Brca1F/F) to test the hypothesis that tissue specific deletion of TP53 and BRCA1 would give rise to tumors reflective of human basal-like breast cancer. In support of our hypothesis, these transgenic mice developed tumors that express basal-like cytokeratins and intrinsic gene expression features similar to human basal-like tumors. Array comparative genomic hybridization revealed a striking conservation of copy number alterations between the K14-Cre; p53F/F Brca1F/F mouse model and human basal-like breast cancer. Conserved events included MYC amplification, KRAS amplification, and RB1 loss. Microarray analysis demonstrated that these DNA copy number events also led to corresponding changes in signatures of pathway activation including high proliferation due to RB1 loss. K14-Cre; p53F/F Brca1F/F also matched human basal-like breast cancer for a proposentity to have immune-cell infiltrates. Given the long latency of K14-Cre; p53F/F Brca1F/F tumors (~250 days), we created tumor syngeneic transplant lines, as well as in vitro cell lines, which were tested for sensitivity to carboplatin and paclitaxel. These therapies invoked acute regression, extended overall survival, and resulted in gene expression signatures of an anti-tumor immune response. These findings demonstrate that this model is a valuable preclinical resource for the study of human basal-like breast cancer.
2019-04-09 | GSE122073 | GEO
Project description:In human basal-like breast cancer, mutations and deletions in TP53 and BRCA1 are frequent oncogenic events. Thus, we interbred mice expressing the CRE-recombinase with mice harboring loxP sites at TP53 and BRCA1 (K14-Cre; p53F/F Brca1F/F) to test the hypothesis that tissue specific deletion of TP53 and BRCA1 would give rise to tumors reflective of human basal-like breast cancer. In support of our hypothesis, these transgenic mice developed tumors that express basal-like cytokeratins and intrinsic gene expression features similar to human basal-like tumors. Array comparative genomic hybridization revealed a striking conservation of copy number alterations between the K14-Cre; p53F/F Brca1F/F mouse model and human basal-like breast cancer. Conserved events included MYC amplification, KRAS amplification, and RB1 loss. Microarray analysis demonstrated that these DNA copy number events also led to corresponding changes in signatures of pathway activation including high proliferation due to RB1 loss. K14-Cre; p53F/F Brca1F/F also matched human basal-like breast cancer for a proposentity to have immune-cell infiltrates. Given the long latency of K14-Cre; p53F/F Brca1F/F tumors (~250 days), we created tumor syngeneic transplant lines, as well as in vitro cell lines, which were tested for sensitivity to carboplatin and paclitaxel. These therapies invoked acute regression, extended overall survival, and resulted in gene expression signatures of an anti-tumor immune response. These findings demonstrate that this model is a valuable preclinical resource for the study of human basal-like breast cancer.
2019-04-09 | GSE122075 | GEO
Project description:Analysis of the effects of an ectopically expressed human SRY (hSRY) on gene expression in the mouse heart. We hypothesize that aberrant expression of the human SRY gene could affect the development and physiology of transgenic mice. To test this hypothesis we have established a Cre-LoxP transgene activation system, thereby activating and expressing the hSRY transgene at the single-cell embryonic stage. Such transgenic mice were born of similar sizes as non-transgenic littermates, but retard in postnatal growth and all die within two weeks of age. To determine the molecular changes associated with such phenotypes, we have analyzed the transcriptomes of hearts of pups expressing (hSRY-ON) and not-expressing (hSRY-OFF) the hSRY transgene. The results provide important information demonstrating that ectopic expression of hSRY resulted in altered expression patterns of numerous genes associating with the development of cardiovascular system and pathogenesis of cardiovascular diseases in the heart.
2017-04-16 | GSE97844 | GEO