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GSE47084
Mus musculus
6 Downloadable Samples
Description
Scl/Tal1 confers hemogenic competence and prevents cardiomyogenesis in embryonic endothelium. Here we show that Scl both directly activates a broad gene regulatory network required for hematopoietic stem/progenitor cell (HS/PC) development, and represses transcriptional regulators required for cardiogenesis. Cardiac repression occurs during a short developmental window through Scl binding to distant cardiac enhancers that harbor H3K4me1 at this stage. Scl binding to hematopoietic regulators extends throughout HS/PC and erythroid development and spreads from distant enhancers to promoters. Surprisingly, Scl complex partners Gata 1 and 2 are dispensable for hematopoietic versus cardiac specification and Scl binding to the majority of its target genes. Nevertheless, Gata factors co-operate with Scl to activate selected transcription factors to facilitate HS/PC emergence from hemogenic endothelium. These results uncover a dual function for Scl in dictating hematopoietic versus cardiac fate choice and suggest a mechanism by which lineage-specific bHLH factors direct the divergence of competing fates.
Publication Title
Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Description
We performed gene expression profile of different B cell populations found in old (18 months old) C57BL/6 female mouse (B1 cells were recovered from both young and old C57BL/6 mice). Mice were nave and healthy (no autoimmunity was detected at the time of the experiment).
Publication Title
Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c⁺ B-cell population is important for the development of autoimmunity.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
Description
Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.
Publication Title
Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
In order to gain a better understanding of Ihh action during embryo implantation, we constitutively activated Smo in the murine uterus using the PRcre mouse model (PRcre/+SmoM2+; SmoM2). Female SmoM2 mice were infertile. They exhibited normal serum progesterone levels and normal ovulation, but ova failed to be fertilized in vivo and the uterus failed to undergo the artificially induced decidual response. SmoM2 mice exhibited uterine hypertrophy. The endometrium had a reduced number of uterine glands and the endometrial stroma lost its normal morphologic characteristics. Microarray analysis of 3 month old SmoM2 uteri demonstrated a chondrocytic signature and confirmed that constitutive activation of SmoM2 increased extracellular matrix production. Thus, constitutive activation of Smo in the mouse uterus alters the extracellular matrix which interferes with early pregnancy.
Publication Title
Constitutive activation of smoothened leads to female infertility and altered uterine differentiation in the mouse.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
Description
Although the induction of C-FOS in the brain has been extensively studied for several decades to date there has been no attempt to identify the targets of C-FOS at a genome wide level, and it was not known how many genes C-FOS activates in a given cell. To identify potential C-FOS target genes, we performed microarray analysis on RNA obtained from mouse cortical (mCTX) neurons infected with lentivirus containing either a control shRNA (targeting firefly luciferase) or c-Fos shRNA that were subsequently depolarized with 0, 1, 3, or 6 hours of KCl.
Publication Title
Genome-wide identification and characterization of functional neuronal activity-dependent enhancers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
Description
The role of Gata2 in regulating uterine function including fertility, implantation, decidualization and P4 signaling in the mouse was investigated by the conditional ablation of Gata2 in the uterus using the (PR-cre) mouse and ChIP-seq for in vivo GATA2 binding sites in the murine uterus upon acute P4 administration.
Publication Title
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Description
Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 15% of all childhood cancer deaths. Patients frequently present at diagnosis with metastatic disease, particularly to the bone marrow. Advances in therapy and understanding of the metastatic process have been limited due in part, to the lack of animal models harboring bone marrow disease. The widely employed transgenic model, the TH-MYCN mouse, exhibits limited metastasis to this site. Here we establish the first genetic immunocompetent mouse model for metastatic neuroblastoma with enhanced secondary tumors in the bone marrow. This model recapitulates two frequent alterations in metastatic neuroblasoma, over-expression of MYCN and loss of caspase-8 expression. In this model, the mouse caspase-8 gene was deleted in neural crest lineage cells by crossing a TH-Cre transgenic mouse with a caspase-8 conditional knockout mouse. This mouse was then crossed with the neuroblastoma prone TH-MYCN mouse. While over-expression of MYCN by itself rarely caused bone marrow metastasis (5% average incidence), combining MYCN overexpression and caspase-8 deletion significantly increased bone marrow metastasis (37% average incidence). Loss of caspase-8 expression did not alter the site, incidence, or latency of the primary tumors. However, secondary tumors were detected in the bone marrow of these mice as early as week 9-10. The mouse model described in this work is a valuable tool to enhance our understanding of metastatic neuroblastoma and treatment options and underscores the role of caspase-8 in neuroblastoma progression.
Publication Title
Th-MYCN mice with caspase-8 deficiency develop advanced neuroblastoma with bone marrow metastasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.
Publication Title
Parthenogenetic stem cells for tissue-engineered heart repair.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 285 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Affymetrix Human Gene 1.1 ST Array profiling of 285 primary medulloblastoma samples.
Publication Title
Subgroup-specific structural variation across 1,000 medulloblastoma genomes.
Sample Metadata Fields
Sex, Age
View Samples