Filters
Technology
Platform
GSE13032
Mus musculus
18 Downloadable Samples
Description
Resiquimod is a nucleoside analog belonging to the imidazoquinoline family of compounds which is known to signal through Toll-like receptor 7. Resiquimod treatment has been demonstrated to inhibit the development of allergen induced asthma in experimental models. Despite this demonstrated effectiveness, little is known about the molecular events responsible for this effect. The aim of the present study was to elucidate the molecular processes which were altered following resiquimod treatment and antigen challenge in a mouse model of allergic asthma. Employing microarray analysis, we have characterized the asthmatic transcriptome of the murine lung and determined that it includes genes involved in: the control of cell cycle progression, airway remodelling, the complement and coagulation cascades, and chemokine signalling. We have demonstrated that systemic resiquimod administration resulted in the recruitment of NK cells to the lungs of the mice, although no causal relationship between NK cell recruitment and treatment efficacy was found. Furthermore, results of our studies demonstrated that resiquimod treatment resulted in the normalization of the expression of genes involved with airway remodelling and chemokine signalling, and in the modulation of the expression of genes including cytokines and chemokines, adhesion molecules, and B-cell related genes, involved in several aspects of immune function and antigen presentation. Overall, our findings identified several genes, important in the development of asthma pathology, that were normalized following resiquimod treatment thus improving our understanding of the molecular consequences of resiquimod treatment in the lung milieu.
Publication Title
Modulation of the allergic asthma transcriptome following resiquimod treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 51 Downloadable Samples
Description
The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined. In a study of target cells and oncogene dosage, we found that Mll-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin- Sca1+ c-kit+) stem cells while committed granulocyte-monocyte progenitors (GMPs) were transformation-resistant and did not cause leukemia. Mll-AF9 was expressed at higher levels in hematopoietic stem (HSC) than GMP cells. Mll- AF9 gene dosage effects were directly shown in experiments where GMPs were efficiently transformed by the high dosage of Mll-AF9 resulting from retroviral transduction. Mll-AF9 up-regulated expression of 196 genes in both LSK and progenitor cells, but to higher levels in LSKs than in committed myeloid progenitors.
Publication Title
Malignant transformation initiated by Mll-AF9: gene dosage and critical target cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Leukemias with MLL-rearrangements are characterized by high expression of the homeo box gene MEIS1. In these studies, we knocked down Meis1 expression by shRNA lentivirus transduction in murine Mll-AF9 leukemia cells. Meis1 knockdown resulted in decreased proliferation and survival of murine Mll-AF9 leukemia cells. We also observed reduced clonogenic capacity and increased monocytic differentiation. The establishment of leukemia in transplant recipients was significantly delayed by Meis1 knockdown. Gene expression profiling of cells transduced with Meis1 shRNA showed reduced expression of genes associated with cell cycle entry and progression. shRNA mediated knockdown of MEIS1 in human MLL-fusion gene leukemia cell lines resulted in reduced cell growth. These results show that MEIS1 expression is important for MLL-rearranged leukemias and suggest that MEIS1 promotes cell cycle entry. Targeting MEIS1 may have therapeutic potential for treating leukemias expressing this transcription factor.
Publication Title
A role for MEIS1 in MLL-fusion gene leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 48 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 48 Downloadable Samples
Description
Analysis of Early Myogenesis Reveals an Extensive Set of Transcriptional Regulators Whose Knock-down Can Inhibit Differentiation
Publication Title
Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation.
Sample Metadata Fields
Cell line, Time
View Samples