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GSE54500
Mus musculus
9 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 12 Downloadable Samples
Description
The leading cause of death in human patients with metastatic renal cell carcinoma (RCC) and malignant cancer in general is the dissemination of the primary tumor to secondary sites. The mechanisms by which RCC colonize the lung microenvironment during metastasis remain largely unknown. To investigate the mechanisms of lung colonization by tumor cells, we grafted human RCC cells with different lung metastatic activities in mice. Gene expression profiling of the mouse lung stromal compartment revealed a gene signature enriched for neutrophil-specific functions, induced preferentially by poorly metastatic cells. Analysis of the gene expression patterns in tumor cells and clinical specimens showed an inverse correlation between metastatic activity and the levels of a number of chemokines, including CXL5 ad IL8. Enforced depletion of CXCL5 and IL8 in tumor cells allowed us to establish a functional link between lung neutrophil infiltration, the secretion of chemokines by cancer cells and metastatic activity. Finally, we showed that human neutrophils displayed a higher cytotoxic activity toward poorly metastatic cells relative to highly metastatic cells. Together, these results support a model in which neutrophils recruited to the lung by tumor-secreted chemokines build an antimetastatic barrier and loss of those neutrophil chemokines in tumor cells is a critical rate-limiting step during lung metastatic seeding.
Publication Title
Neutrophil chemokines secreted by tumor cells mount a lung antimetastatic response during renal cell carcinoma progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Description
Affymetric arrays were performed on thyroid samples collected from GEMMs: Cre-negative, Tpo-cre;HrasG12V (Homozygous), Tpo-cre;HrasG12V,p53f/f (PDTC), Tpo-cre;HrasG12V,p53f/f (ATC)
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Aberrant Hox gene activation is a recurrent feature in several different types of human leukemia, including leukemias with rearrangements of the mixed lineage leukemia (MLL) gene. In this study, we demonstrate that Hox gene expression is controlled by higher degree H3K79 methylation in acute myeloid leukemia (AML). We show that the deposition of progressive H3K79 methylation states at the genomic loci of critical Hox genes is dependent on the interaction of the H3K79 methyltransferase Dot1l with Af10, a protein that is found in the Dot1l complex isolated from diverse cell types. Furthermore, abrogation of the Dot1l-Af10 interaction reverses aberrant epigenetic profiles found in the leukemia epigenome and impairs the transforming ability of mechanistically distinct AML oncogenes.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Comparison of polysomal profiles of murine adult olig2 cortical progenitors, murine tumor olig2 cells derived from hPDGF-B-driven glioblastomas, and murine olig2 proliferative recruited glioma cells contributing to the tumor mass but not derived from the cell of origin
Publication Title
Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
During development, a polarized sheet of epidermal cells undergoes stratification and differentiation to produce the skin barrier. Through mechanisms poorly understood, the process involves adhesion and Notch signaling. To elucidate how epidermal embryogenesis is governed, we conditionally targeted transcription factor serum response factor (SRF), which has been shown to be essential for proper epidermal differentiation in vitro and in vivo. Seeking mechanism, we identified actomyosin-related genes as well-known SRF targets downregulated shortly after ablation. We show that this results in a diminished cortical actomyosin network which fails to regulate the transition of cells from the basal proliferative layer to the suprabasal differentiating layer resulting in an inability of cells to properly execute stratification and differentiation.
Publication Title
Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Description
We used microarrays to detail the global programme of gene expression dependent upon Stat3 in regulatory T cells
Publication Title
CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
The main cell of origin of the Sonic hedgehog (SHH) subgroup of medulloblastoma (MB) is granule cell precursors (GCPs), a SHH-dependent transient amplifying population in the developing cerebellum. SHH-MBs can be further subdivided based on molecular and clinical parameters, as well as location since SHH-MBs occur preferentially in the lateral cerebellum (hemispheres). Our analysis of adult patient data suggests that tumors with Smoothened (SMO) mutations form more specifically in the hemispheres than those with Patched 1 (PTCH1) mutations. Using sporadic mouse models of SHH-MB with the two mutations commonly seen in adult MB, constitutive activation of Smo (SmoM2) or loss-of-Ptch1, we found that regardless of timing of induction or type of mutation, tumors developed primarily in the hemispheres with SmoM2-mutants indeed showing a stronger specificity. We further uncovered that GCPs in the hemispheres are more susceptible to high level SHH signaling compared to GCPs in the medial cerebellum (vermis), as more SmoM2 or Ptch1-mutant hemisphere cells remain undifferentiated and show increased tumorigenicity when transplanted. Finally, we identified location-specific GCP gene expression profiles, and found that deletion of the genes most highly expressed in the hemispheres (Nr2f2) or vermis (Engrailed1) showed opposing effects on GCP differentiation. Our studies thus provide new insights into intrinsic differences within GCPs that impact on SHH-MB progression.
Publication Title
Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
The generation of induced pluripotent stem cells (iPSCs) often results in aberrant silencing of the imprinted Dlk1-Dio3 gene cluster, which compromises their ability to generate entirely iPSC-derived mice (all-iPSC mice). Here, we show that reprogramming in the presence of ascorbic acid attenuates hypermethylation of Dlk1-Dio3 by enabling a chromatin configuration at its imprint control region that interferes with abnormal binding of the DNA methyltransferase Dnmt3a. This approach allowed us to generate adult all-iPSC mice from mature B cells, which have thus far failed to support the development of exclusively iPSC-derived postnatal mice. Our data demonstrate that factor-mediated reprogramming can endow a defined, terminally differentiated cell type with a developmental potential equivalent to that of embryonic stem cells. More generally, these findings indicate that the choice of culture conditions used for transcription factor-mediated reprogramming can strongly influence the epigenetic and biological properties of resultant iPSCs.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
The RB and p53 tumor suppressor pathways regulate the transcription of genes involved in cell cycle progression, DNA replication, DNA repair, and apoptosis. These tumor suppressors are critical modulators of the response to genotoxic damage and both pathways are frequently inactivated in human cancers.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples