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GSE12881
Mus musculus
5 Downloadable Samples
Description
Here, we show that functional loss of a single gene is sufficient to confer constitutive milk protein production and protection against mammary tumor formation. Caveolin-3 (Cav-3), a muscle-specific caveolin-related gene, is highly expressed in striated and smooth muscle cells. We demonstrate that Cav-3 is also expressed in myoepithelial cells within the mammary gland. To determine if genetic ablation of Cav-3 expression affects adult mammary gland development, we next studied the phenotype(s) of Cav-3 (-/-) null mice. Interestingly, detailed analysis of Cav-3 (-/-) virgin mammary glands shows dramatic increases in ductal thickness, side-branching, and the development of extensive lobulo-alveolar hyperplasia, akin to the changes normally observed during pregnancy and lactation. Analysis by genome-wide expression profiling reveals the upregulation of gene transcripts associated with pregnancy/lactation, mammary stem cells, and human breast cancers, consistent with a constitutive lactogenic phenotype. The expression levels of three key transcriptional regulators of lactation, namely Elf5, Stat5a, and c-Myc are also significantly elevated. Experiments with pregnant mice directly show that Cav-3 (-/-) mice undergo precocious lactation. Finally, using orthotopic implantation of a transformed mammary cell line (known as Met-1), we demonstrate that virgin Cav-3 (-/-) mice are dramatically protected against mammary tumor formation. Interestingly, Cav-3 (+/-) mice also show similar protection, indicating that even reductions in Cav-3 levels are sufficient to render these mice resistant to tumorigenesis. Thus, Cav-3 (-/-) mice are a novel preclinical model to study the protective effects of a constitutive lactogenic microenviroment on mammary tumor onset and progression. Our current studies have broad implications for using the lactogenic micro-environment as a paradigm to discover new therapies for the prevention and/or treatment of human breast cancers. Most importantly, a lactation-based therapeutic strategy would provide a more natural and nontoxic approach to the development of novel anti-cancer therapies.
Publication Title
Loss of caveolin-3 induces a lactogenic microenvironment that is protective against mammary tumor formation.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
The E-protein transcription factors E2A and HEB play important roles at several stages of hematopoiesis. However, the exact mechanism for theire action and the main targets in the LY6D negative common lymphoid progentior (CLP) compartment remains unknown. By adressing this question, we will gain important infromation regarding the early events leading to B-cell specification.
Publication Title
The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor.
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Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Recent studies have documented genome-wide binding patterns of transcriptional regulators and their associated epigenetic marks in hematopoietic cell lineages. In order to determine how epigenetic marks are established and maintained during developmental progression, we have generated long-term cultures of hematopoietic progenitors by enforcing the expression of the E-protein antagonist Id2. Hematopoietic progenitors that express Id2 are multipotent and readily differentiate upon withdrawal of Id2 expression into committed B lineage cells, thus indicating a causative role for E2A (Tcf3) in promoting the B cell fate. Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid enhancers are premarked by the poised or active enhancer mark H3K4me1 in multipotent progenitors. Thus, in hematopoietic progenitors, multilineage priming of enhancer elements precedes commitment to the lymphoid or myeloid cell lineages.
Publication Title
Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Recent studies have documented genome-wide binding patterns of transcriptional regulators and their associated epigenetic marks in hematopoietic cell lineages. In order to determine how epigenetic marks are established and maintained during developmental progression, we have generated long-term cultures of hematopoietic progenitors by enforcing the expression of the E-protein antagonist Id2. Hematopoietic progenitors that express Id2 are multipotent and readily differentiate upon withdrawal of Id2 expression into committed B lineage cells, thus indicating a causative role for E2A in promoting the B cell fate. Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid enhancers are pre-marked by H3K4me1 in multipotent progenitors. However, H3K4me1 levels at a subset of enhancers are elevated during developmental progression, resulting in evolving enhancer repertoires that we propose orchestrate the myeloid and B cell fates.
Publication Title
Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Epithelial Hedgehog (Hh) ligands regulate several aspects of fetal intestinal organogenesis and emerging data implicate the Hh pathway in inflammatory signaling in adult colon. We investigated the effects of chronic Hh inhibition in vivo and profiled molecular pathways acutely modulated by Hh signaling in the intestinal mesenchyme.
Publication Title
Hedgehog is an anti-inflammatory epithelial signal for the intestinal lamina propria.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Although Notch signaling has been clearly implicated in lymphoid differentiation, its role in myeloid lineages differentiation is unclear.
Publication Title
Notch signaling specifies megakaryocyte development from hematopoietic stem cells.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 16 Downloadable Samples
IlluminaHiSeq2500
Description
wt1a:GFP labels a population of subepicardial cells in the uninjured ventricle. Here we compare the expression profile of wt1a:GFP-positive cells to the rest of the cells of the ventricle. Overall design: Four paired biological replicates of wt1a:GFP-positive and wt1a:GFP-negative cells obtained from pools of 3-5 zebrafish heart ventricles.
Publication Title
Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Down syndrome is the most common form of genetic mental retardation. How Trisomy 21 causes mental retardation remains unclear and its effects on adult neurogenesis have not been addressed. To gain insight into the mechanisms causing mental retardation we used microarrays to investigate gene expression differences between Ts1Cje (a mouse model of Down syndrome) and C57BL/6 littermate control neurospheres. The neurospheres were generated from neural stem cells and progenitors isolated from the lateral walls of the lateral ventricles from adult mice.
Publication Title
Gene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome.
Alternate Accession IDs
Sample Metadata Fields
Sex, Disease
View Samples- Mus musculus
- 23 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Danio rerio
- 23 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Unlike human hearts, zebrafish hearts efficiently regenerate after injury. Regeneration is driven by the strong proliferation response of its cardiomyocytes to injury. In this study, we show that active telomerase is required for cardiomyocyte proliferation and full organ recovery, supporting the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction. Overall design: Heart transcriptomes of WT and telomerase defective adult zebrafish animals were profiled by RNASeq, in control conditions and 3 days after heart cryoinjury.
Publication Title
Telomerase Is Essential for Zebrafish Heart Regeneration.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
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