Filters
Technology
Platform
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cardiac hypertrophy is regulated by the zinc finger-containing DNA binding factors Gata4 and Gata6, both of which are required to mount a productive growth response of the adult heart. To determine if Gata4 and Gata6 are redundant or have non-overlapping roles, we performed cardiomyocyte-specific conditional gene deletions for Gata4 and Gata6 in conjunction with reciprocal replacement with a transgene encoding either Gata4 or Gata6, during the pressure overload response. We determined that Gata4 and Gata6 play a redundant and dosage-sensitive role in programming the hypertrophic growth response itself following pressure overload stimulation. However, non-redundant functions were identified as functional decompensation induced by either Gata4 or Gata6 deletion was not rescued by the reciprocal transgene, and only Gata4 heart-specific deletion produced a reduction in capillary density after pressure overload. Gene expression profiling from hearts of these gene-deleted mice showed both overlapping and unique transcriptional codes, with Gata4 exhibiting the strongest impact. These results indicate that Gata4 and Gata6 play a dosage-dependent and semi-redundant role in programming cardiac hypertrophy, but that each has a unique role in maintaining cardiac homeostasis and adaptation to injury that cannot be compensated by the other.
Publication Title
Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
In order to identify targets for HDAC4, NRVM were infected with adenoviral vectors encoding beta-Galactosidase or Flag- HDAC4, and incubated in serum free or 10% fetal calf serum containing growth medium for 48 hrs.
Publication Title
Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Serine 105 phosphorylation of GATA4 is necessary for stress-induced cardiac hypertrophy in vivo.
Publication Title
Serine 105 phosphorylation of transcription factor GATA4 is necessary for stress-induced cardiac hypertrophy in vivo.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Overall goal: To elucidate the endothelial-specific role of Gata4 signaling in endothelial maturation and vascular maintenance. Purpose of analysis: To generate a transcriptional profile of Gata4-deficient endothelial cells in the adult myocardium under homeostatic conditions. Overall design: Experimental structure: Transcriptional profile generated using RNAseq and differential gene expression analyses of endothelial cells lacking Gata4 isolated from healthy hearts.
Publication Title
Gata4-Dependent Differentiation of c-Kit<sup>+</sup>-Derived Endothelial Cells Underlies Artefactual Cardiomyocyte Regeneration in the Heart.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 185 Downloadable Samples
- Illumina HiSeq 2500
Description
Cardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell-type in terms of their origins and functional effects in vivo. Methods: Here we generate Postn (periostin) gene-targeted mice containing a tamoxifen inducible Cre for cellular lineage tracing analysis. This Postn allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Results: Lineage tracing with 4 additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin+ myofibroblasts reduces collagen production and scar formation after myocardial infarction. Periostin-traced myofibroblasts also revert back to a less activated state upon injury resolution. Conclusions: Our results define the myofibroblast as a periostin-expressing cell-type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21+ tissue-resident fibroblasts. Overall design: Fluidigm C1 whole genome transcriptome analysis of lineage mapped cardiac myofibroblasts
Publication Title
Genetic lineage tracing defines myofibroblast origin and function in the injured heart.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina HiSeq 2500
Description
Normal development requires tight regulation of cell proliferation and cell death. Here, we investigated these control mechanisms in the hyaloid vessels, a temporary vascular network in the mammalian eye that requires a Wnt/ß-catenin response for scheduled regression. Transcriptome analysis of the postnatal day 5 mouse hyaloid showed expression of several Wnt pathway proteins. We investigated whether the hyaloid Wnt response was linked to the oncogene Myc, and the cyclin-dependent kinase inhibitor P21 (CDKN1A), both established regulators of cell cycle progression and cell death. Our analysis showed that the Wnt pathway coreceptors LRP5 and LRP6 have overlapping activities mediating the Wnt/ß-catenin signaling in hyaloid vascular endothelial cells (VECs). We also showed that both Myc and Cdkn1a are downstream of the Wnt response and are required for hyaloid regression but for different reasons. Conditional deletion of Myc in VECs suppressed both proliferation and cell death. By contrast, conditional deletion of Cdkn1a resulted in VEC over-proliferation that countered the effects of cell death on regression. When combined with analysis of MYC, and P21 protein levels, this analysis suggests that a Wnt/ß-catenin, MYC-P21 pathway regulates scheduled hyaloid vessel regression. Overall design: Hyaloid vascular preparations from postnatal day 5 mice were harvested in cold PBS and RNA extracted in Tri Reagent. RNA amplifcation was performed on total RNA before cDNA library was made. Samples were then sequenced using Illimina HiSeq2500 to obtain 25-30 million paired-end reads.
Publication Title
Developmental vascular regression is regulated by a Wnt/β-catenin, MYC and CDKN1A pathway that controls cell proliferation and cell death.
Sample Metadata Fields
Specimen part, Subject
View Samples
GSE23028- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To identify differences in gene expression between peptidylprolyl isomerase F (cyclophilin D; Ppif)-null hearts and WT control hearts.
Publication Title
Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Normal erythropoiesis requires a critical balance between proapoptotic and antipaoptotic pathways. Bcl-xl, an antiapoptotic protein is induced at end-stages of differentiation of erythroid precursors in response to erythropoietin. The details of the proapoptotic pathway and the critical proapoptotic proteins inhibited by Bcl-xl in erythropoiesis are not well understood. We employed gene targeting to ablate Nix, a proapoptotic BH3-domain only Bcl2 family protein, which is known to be transcriptionally induced during erythropoiesis. Nix null mice exhibited reticulocytosis and thrombocytosis in the peripheral blood; and profound splenomegaly with erythroblastosis in the spleen and bone marrow despite normal erythropoietin levels and blood oxygen tension. In vivo apoptosis was diminished in erythroblast precursors from Nix null spleens. To define the molecular consequences of Nix ablation on apoptosis and erythropoiesis, we conducted a detailed comparative analysis of gene expression in spleens from 8 week old Nix null mice and wild type controls. Of 45,101 genes analyzed, 514 were significantly upregulated and 386 down-regulated in Nix-/- splenocytes. Functional cluster analysis delineated the ten most highly regulated gene sets, revealing increased levels of cell cycle and erythroid genes, with decreased levels of cell death and B-cell genes.
Publication Title
Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human B cell lineage acute lymphoblastic leukemia (ALL) cells carrying MLL-AF4 (SEM; BEL) and E2A-PBX1 (697) gene rearrangements were transduced with the mouse ecotropic receptor to permit subsequent entry of retroviral BCR-ABL1 GFP and GFP empty vectors (EV) pseudotyped with murine ecotropic envelope. GFP expression was measured by flow cytometry. Transductions with BCR-ABL1 GFP and GFP empty vectors (EV) were performed in the presence and absence of 2 mmol/l Imatinib (TKI). Washout of Imatinib in one series of experiments is indicated with an arrow. To study gene expression changes in MLL-AF4 and E2A-PBX1 B cell lineage ALL cells that were transduced with empty vectors (EV), BCR-ABL1 GFP in the presence of Imatinib (BCR-ABL1 OFF), washout of Imatinib (BCR-ABL1 ON) and subsequent re-addition of Imatinib, microarray analyses were performed.
Publication Title
Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Global deficiency of catalytic subunit Ppp3cb, and tissue-specific ablation of regulatory subunit Ppp3r1 from skeletal muscle but not adipose tissue or liver led to protection from high-fat diet induced obesity and comorbid sequel.
Publication Title
Calcineurin Links Mitochondrial Elongation with Energy Metabolism.
Sample Metadata Fields
Sex, Specimen part
View Samples