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GSE51250
Mus musculus
9 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Combined targeting of JAK2 and Bcl-2/Bcl-xL to cure mutant JAK2-driven malignancies and overcome acquired resistance to JAK2 inhibitors.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 15 Downloadable Samples
Description
Notch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Publication Title
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Mus musculus
- 20 Downloadable Samples
Description
The objective is to identify genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by the Rag proteins in murine pre-B cells. Cells lacking Artemis are used since the Rag-induced DSBs will not be repaired and, thus, will provide a continuous stimulus to the cell. Cells lacking Artemis and Atm are used to determine which gene expression changes depend on Atm and cells lacking Artemis that express an I kappa B alpha dominant negative are used to determine which gene expression changes depend on NFkB.
Publication Title
DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 41 Downloadable Samples
Description
Prions consist of aggregates of abnormal conformers of cellular prion protein (PrPC). They propagate by recruiting host-encoded PrPC although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrPC expression differences, to identify such factors. We examined the transcriptomes of prion-resistant revertants, isolated from highly susceptible cells, and identified a gene expression signature associated with susceptibility. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease-related PrP deposits. Loss-of-function of nine of these genes significantly increased susceptibility. Remarkably, inhibition of fibronectin 1 binding to integrin 8 by RGD peptide inhibited metalloproteinases (MMP)-2/9 whilst increasing prion propagation rates. This indicates that prion replication may be controlled by MMPs at the ECM in an integrin-dependent manner.
Publication Title
Identification of a gene regulatory network associated with prion replication.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Human and mouse blood each contain two monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two species subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPAR signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse.
Publication Title
Comparison of gene expression profiles between human and mouse monocyte subsets.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Regulatory T cells (Tregs) can suppress a wide variety of cell types, in diverse organ sites and inflammatory conditions. While Tregs possess multiple suppressive mechanisms, the number required for maximal function is unclear. Furthermore, whether any inter-relationship orcross-regulatory mechanisms exist that areused to orchestrate and control their utilization is unknown. Here we assessed the functional capacity of Tregs lacking the ability to secrete both interleukin-10 (IL-10) and IL-35, which individually are required for maximal Treg activity. Surprisingly, IL-10/IL-35-double deficient Tregswere fully functionalin vitro and in vivo. Loss of IL-10 and IL-35 was compensated for by a concurrent increase in cathepsin E (CTSE) expression, enhanced TRAIL (Tnfsf10)expression and soluble TRAIL release, rendering IL-10/IL-35-double deficient Tregsfunctionally dependent on TRAIL in vitro and in vivo. Lastly, while C57BL/6 Tregs are IL-10/IL-35-dependent, Balb/c Tregs, which express high levels of CTSE and enhanced TRAIL expression, are TRAIL-dependent.These data reveal that cross-regulatory pathways exist, which control the utilization of suppressive mechanisms,thereby providing Tregfunctional plasticity.
Publication Title
The plasticity of regulatory T cell function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 47 Downloadable Samples
Description
Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here, we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature, and nerves are specified and the musculoskeletal system of the limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore-limb and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which tampers off at later time points. Among 3520 genes identified as significantly up-regulated in the limb, we find ~30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that correlate with functional programs during limb development and are likely to provide new insights into specific tissue patterning processes. Here we provide for the first time, a comprehensve analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis.
Publication Title
Global gene expression analysis of murine limb development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA-mRNA interactions in a murine model of hyperoxia-induced bronchopulmonary dysplasia.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The restoration of catalytic activity to mutant enzymes by small molecules is well-established for in vitro systems. Here we show that the protein tyrosine kinase Src R388A mutant can be rescued in live cells using the small molecule imidazole. Cellular rescue of a v-Src homolog was rapid and reversible and conferred predicted oncogenic properties. Using chemical rescue in combination with mass spectrometry, six known Src kinase substrates were confirmed, and several new protein targets identified. Chemical rescue data suggests that c-Src is active under basal conditions. Rescue of R388A c-Src also allowed contributions of Src to the MAP kinase pathway to be clarified. This chemical rescue approach is likely to be of broad utility in cell signaling.
Publication Title
Chemical rescue of a mutant enzyme in living cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
BACKGROUND: p53 is an important tumor suppressor with a known role in the later stages of colorectal cancer, but its relevance to the early stages of neoplastic initiation remains somewhat unclear. Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated.
Publication Title
A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine.
Sample Metadata Fields
Specimen part
View Samples