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GSE20398
Mus musculus
30 Downloadable Samples
Description
Numerous studies have established a critical role for BMP signaling in skeletal development. In the developing axial skeleton, sequential SHH and BMP signals are required for specification of a chondrogenic fate in somitic tissue. A similar paradigm is thought to operate in the limb, but the signals involved are unclear. To investigate the nature of these signals we examined BMP action in mesenchymal populations derived from the early murine limb bud (~ E10.5). These populations exhibited a graded response to BMPs, in which early limb mesenchymal (EL) cells (from the distal hind limb) displayed an anti-chondrogenic response, whereas BMPs promoted chondrogenesis in older cell populations. To better understand the molecular basis of disparate BMP action in these various populations, gene expression profiling with Affymetrix microarrays was employed to identify BMP-regulated genes. These analyses showed that BMPs induced a distinct gene expression pattern in the EL cultures versus later mesenchymal limb populations (IM and LT).
Publication Title
Regulation of BMP-dependent chondrogenesis in early limb mesenchyme by TGFbeta signals.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 4 Downloadable Samples
IlluminaHiSeq4000
Description
We report high-throughput profiling of gene expression from whole zebrafish ventricles. We profile mRNA in uninjured ventricles and those undergoing regeneration 14 days after genetic ablation. This study provides a framework for understanding transcriptional changes during adult models of regeneration. Overall design: Examination of gene expression in cardiomyocytes under different states of proliferation.
Publication Title
Resolving Heart Regeneration by Replacement Histone Profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
Description
Helicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) and non-progenitor gastric epithelial cells (npGECs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma.
Publication Title
Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Most tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial (iBMK) cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity and contact inhibition, while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila.
Publication Title
Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 40 Downloadable Samples
Description
This represents an unbiased evaluation of the transcriptional response in the prefrontal cortex and hippocampus areas in the Df(16)A/+ mice, a mouse model of human 22q11 microdeletion syndrome. These mice were generated by chromosomal engineering and carry a microdeltion of ~1.3Mb in the mouse locus syntenic to the human 22q11.1
Publication Title
Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Brain-derived serotonin favors appetite in mice following its binding to the Htr1a and Htr2b receptors in arcuate neurons of the hypothalamus. In this study, we identified that CREB is the transcriptional effector of brain-derived serotonin control of appetite in arcuate nuclei.
Publication Title
Leptin-dependent serotonin control of appetite: temporal specificity, transcriptional regulation, and therapeutic implications.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
Description
Aims: We investigate sex differences and the role of oestrogen receptor beta (ERbeta) in a mouse model of pressure overload-induced myocardial hypertrophy. Methods and results: We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ERbeta knockout (ERbeta-/-) C57Bl6 mice. All mice were characterised by echocardiography and haemodynamic measurements and were sacrificed nine weeks after surgery. Left ventricular (LV) samples were analysed by microarray profiling, real-time RT-PCR and histology. After nine weeks, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. These sex differences were abolished in ERbeta-/- mice. ERbeta deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that male WT hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than female hearts. ERbeta-/- mice exhibited a different transcriptome. Induction of pro-apoptotic genes after TAC occurred in ERbeta-/- mice of both sexes with a stronger expression in ERbeta-/- males. Histological analysis revealed, that cardiac fibrosis was more pronounced in male WT TAC than in female mice. This was abolished in ERbeta-/- mice. Apoptosis was significantly induced in both sexes of ERbeta-/- TAC mice, but it was most prominent in males. Conclusion: Female sex offers protection against ventricular chamber dilation in the TAC model. Both the female sex and ERbeta attenuate the development of fibrosis and apoptosis; thus slowing the progression to heart failure.
Publication Title
Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
Description
Epigenetic modifications must underlie lineage-specific differentiation since terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Hematopoiesis provides a well-defined model of progressive differentiation in which to study the role of epigenetic modifications in cell fate decisions. Multi-potent progenitors (MPPs) can differentiate into all blood cell lineages, while downstream progenitors commit to either myeloerythroid or lymphoid lineages. While DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs {Broske, 2009 #6}, a comprehensive DNA methylation map of hematopoietic progenitors, or of any cell lineage, does not exist. Here we have generated a mouse DNA methylation map, examining 4.6 million CpG sites throughout the genome including all CpG islands and shores, examining MPPs, all lymphoid progenitors (ALPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Interestingly, differentiation towards the myeloid lineage corresponds with a net decrease in DNA methylation, while lymphoid commitment involves a net increase in DNA methylation, but both show substantial dynamic changes consistent with epigenetic plasticity during development. By comparing lineage-specific DNA methylation to gene expression array data, we find many examples of genes and pathways not previously known to be involved in lymphoid/myeloid differentiation, such as Gcnt2, Arl4c, Gadd45, and Jdp2. Several transcription factors, including Meis1 and Prdm16 were methylated and silenced during differentiation, suggesting a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome appears to be important in hematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation, often correlating with gene expression changes, and define a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions.
Publication Title
Comprehensive methylome map of lineage commitment from haematopoietic progenitors.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 14 Downloadable Samples
Description
The gastrointestinal tract of mammals is inhabited by hundreds of distinct species of commensal microorganisms that exist in a mutualistic relationship with the host. The process by which the commensal microbiota influence the host immune system is poorly understood. We show here that colonization of the small intestine of mice with a single commensal microbe, segmented filamentous bacterium (SFB), is sufficient to induce the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere tightly to the surface of epithelial cells in the terminal ileum of mice with Th17 cells but are absent from mice that have few Th17 cells. Colonization with SFB was correlated with increased expression of genes associated with inflammation, anti-microbial defenses, and tissue repair, and resulted in enhanced resistance to the intestinal pathogen Citrobacter rodentium. Control of Th17 cell differentiation by SFB may thus establish a balance between optimal host defense preparedness and potentially damaging T cell responses. Manipulation of this commensal-regulated pathway may provide new opportunities for enhancing mucosal immunity and treating autoimmune disease.
Publication Title
Induction of intestinal Th17 cells by segmented filamentous bacteria.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Extensive molecular profiling of leukemias and preleukemic diseases has revealed that distinct clinical entities, like acute myeloid (AML) and T-lymphoblastic leukemia, share the same pathogenetic mutations. It is not well understood how the cell of origin, accompanying mutations, extracellular signals or structural differences in a mutated gene determine the phenotypic identity of the malignant disease. We studied the relationship of different protein domains of the MN1 oncogene and their effect on the leukemic phenotype, building on the ability of MN1 to induce leukemia without accompanying mutations. We found that the most C-terminal domain of MN1 was required to block myeloid differentiation at an early stage, and deletion of an extended C-terminal domain resulted in loss of myeloid identity and cell differentiation along the T-cell lineage in vivo. Megakaryocytic/erythroid lineage differentiation was blocked by the most N-terminal domain. In addition, the N-terminus was required for proliferation and leukemogenesis in vitro and in vivo through upregulation of HoxA9, HoxA10 and Meis2. Our results provide evidence that a single oncogene can modulate cellular identity of leukemic cells based on its active domains. It is therefore likely that different mutations in the same oncogene may impact cell fate decisions and phenotypic appearance of malignant diseases.
Publication Title
Cell fate decisions in malignant hematopoiesis: leukemia phenotype is determined by distinct functional domains of the MN1 oncogene.
Sample Metadata Fields
Specimen part
View Samples