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Mus musculus
6 Downloadable Samples
Description
Interleukin-33 (IL-33) is elevated in afflicted tissues of patients with mast cell-dependent chronic allergic diseases. Based on its acute effects on mouse mast cells (MCs), IL-33 is thought to play a role in the pathogenesis of allergic disease through MC activation. However, the manifestations of chronic IL-33 exposure on human MC function, which best reflect the conditions associated with chronic allergic disease, are unknown. We now find that long-term exposure of human and mouse MCs to IL-33 results in a substantial reduction of MC activation in response to antigen. This reduction required >72 h exposure to IL-33 for onset and 1-2 wk for reversion following IL-33 removal. This hypo-responsive phenotype was determined to be a consequence of MyD88-dependent attenuation of signaling processes necessary for MC activation including antigen-mediated calcium mobilization and cytoskeletal reorganization; potentially as a consequence of down-regulation of the expression of PLCg1 and Hck. These findings suggest that IL-33 may play a protective, rather than a causative role in MC activation under chronic conditions and, furthermore, reveal regulated plasticity in the MC activation phenotype. The ability to down-regulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease.
Publication Title
IL-33 induces a hyporesponsive phenotype in human and mouse mast cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 17 Downloadable Samples
Description
The capacity of the hematopoietic system to promptly respond to peripheral demands relies on adequate pools of progenitors able to transiently proliferate and differentiate in a regulated manner. However, little is known about factors that may restrain progenitor maturation to maintain their reservoirs. In addition to a profound defect in hematopoietic stem cell (HSC) self-renewal, conditional knockout mice for the Pbx1 proto-oncogene have a significant reduction in lineage-restricted progenitors, including common myeloid progenitors (CMPs) and, to a lesser extent, granulocyte-monocyte progenitors (GMPs).
Publication Title
Pbx1 restrains myeloid maturation while preserving lymphoid potential in hematopoietic progenitors.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 38 Downloadable Samples
Description
The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Normal myeloid lineage cell populations (C57BL/6 mice, aged 4-10 weeks, male or female) with three distinct immunophenotypes were prospectively isolated and characterized. In preparation for FACS sorting, bone marrow cells were separated into c-kit+ and c-kit- fractions using an AutoMACS device. C-kit+ cells were further fractionated based on Gr1 and Mac1 expression, and absence of lineage antigen expression (B220, TER119, CD3, CD4, CD8 and IL7R), by cell sorting. C-kit+ Gr1+ Mac1lo/- and c-kit+ Gr1+ Mac1+ displayed cytologic features of undifferentiated hematopoietic cells or myeloblasts, whereas c-kit- Gr1+ Mac1+ cells were mature neutrophils.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Leukemia cells from mice with MLL-AF10 AML were fractionated into separate sub-populations on the basis of c-kit expression, which correlates with MLL LSC frequency (Somervaille and Cleary, 2006). The sorted AML sub-populations exhibited substantial differences in their frequencies of AML CFCs/LSCs (mean 14-fold) and morphologic features, consistent with a leukemia cell hierarchy with maturation through to terminally differentiated neutrophils.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Box C/D-type small nucleolar RNAs (snoRNAs) are functional RNAs responsible for mediating 2-O-ribose methylation of ribosomal RNAs (rRNAs) within the nucleolus. Previously, in relation to a novel chromosomal translocation in a human B-cell lymphoma, we identified U50HG, a non-protein-coding gene that hosted a box C/D-type U50 snoRNA within its intron. To investigate the physiological importance of the U50 snoRNA and its involvement in tumorigenesis, we generated a mouse model deficient in mouse U50 (mU50) snoRNA expression without altering the expression of mouse mU50 host-gene, mU50HG-b. The established mU50 snoRNA-deficient mice showed a significant reduction of mU50 snoRNA expression and the corresponding target rRNA methylation in various organs. Lifelong phenotypic monitoring showed that the mU50-deficient mice looked almost normal without accelerated tumorigenicity; however, a notable difference was the propensity for anomalies in the lymphoid organs.
Publication Title
Generation of a mouse model with down-regulated U50 snoRNA (SNORD50) expression and its organ-specific phenotypic modulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Neutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis of S. aureus-infected skin revealed that induction of neutrophil recruitment genes was largely dependent upon IL-1beta/IL-1R activation. Unexpectedly, using IL 1beta reporter mice, neutrophils were identified as the primary source of IL-1beta at the site of infection. Furthermore, IL-1beta-producing neutrophils were necessary and sufficient for abscess formation and bacterial clearance. S. aureus-induced IL 1beta production by neutrophils required TLR2, NOD2, FPRs and the ASC/NLRP3 inflammasome. Taken together, IL-1beta and neutrophil abscess formation during an infection are functionally, spatially and temporally linked as a consequence of direct IL-1beta production by neutrophils.
Publication Title
Neutrophil-derived IL-1β is sufficient for abscess formation in immunity against Staphylococcus aureus in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Target genes of Fbxl10 during 3T3-L1 adipogenesis was analyzed
Publication Title
The FBXL10/KDM2B scaffolding protein associates with novel polycomb repressive complex-1 to regulate adipogenesis.
Sample Metadata Fields
Cell line, Treatment
View Samples
GSE33516- Mus musculus
- 2 Downloadable Samples
Description
We used microarray analysis to identify specific molecular mechanisms controlling IL-5 transcription in memory Th2 cells.
Publication Title
Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples