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GSE24489
Mus musculus
13 Downloadable Samples
Description
The expression of the small molecular weight heat shock protein (Hsp) H11 kinase/Hsp22 (Hsp22) is restricted to a limited number of tissues, including the heart and skeletal muscle, both in rodents and in humans. We generated a mouse knockout (KO) model, and investigated the role of Hsp22 in regulating cardiac hypertrophy in response to pressure overload. We compared gene expression profiles between WT and KO mice in basal condition and three days pressure overload after transverse aortic constriction (TAC). These data illustrated a novel mechanism of Hsp22-related gene expression in response to cardiac stress.
Publication Title
H11 kinase/heat shock protein 22 deletion impairs both nuclear and mitochondrial functions of STAT3 and accelerates the transition into heart failure on cardiac overload.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
GDAP1 is a mitochondrial fission factor and mutations in GDAP1 cause Charcot-Marie-Tooth disease. Gdap1 knockout mice, mimicking genetic alterations of patients suffering from severe CMT forms, develop an age-related, hypomyelinating peripheral neuropathy.
Publication Title
The Gdap1 knockout mouse mechanistically links redox control to Charcot-Marie-Tooth disease.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Knockdown of the transcription factor PU.1 (Spi1) leads to acute myeloid leukemia (AML) in mice. We examined the transcriptome of PU.1 knockdown hematopoietic stem cells (HSC) in the preleukemic phase by linear amplification and genome-wide array analysis to identify transcriptional changes preceding malignant transformation. Hierarchical cluster analysis and principal component analysis clearly distinguished PU.1 knockdown from wildtype HSC. Jun family transcription factors c-Jun and JunB were among the top downregulated targets. Retroviral restoration of c-Jun expression in bone marrow cells of preleukemic mice partially rescued the PU.1-initiated myelomonocytic differentiation block. Lentiviral restoration of JunB at the leukemic stage led to reduced clonogenic growth, loss of leukemic self-renewal capacity, and prevented leukemia in transplanted NOD-SCID mice. Examination of 305 AML patients confirmed the correlation between PU.1 and JunB downregulation and suggests its relevance in human disease. These results delineate a transcriptional pattern that precedes the leukemic transformation in PU.1 knockdown HSC and demonstrate that decreased levels of c-Jun and JunB contribute to the development of PU.1-induced AML by blocking differentiation (c-Jun) and increasing self-renewal (JunB). Therefore, examination of disturbed gene expression in HSC can identify genes whose dysregulation is essential for leukemic stem cell function and are targets for therapeutic interventions.
Publication Title
Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 22 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
Description
Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients. The expression of PKC-II and the subsequent activation of NF-B in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC- knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-II- NF-B signaling pathway in the tumor microenvironment. Upregulated stromal PKC-II in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies.
Publication Title
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients. The expression of PKC-II and the subsequent activation of NF-B in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC- knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-II- NF-B signaling pathway in the tumor microenvironment. Upregulated stromal PKC-II in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies.
Publication Title
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Sample Metadata Fields
Specimen part, Disease stage, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Transgenic expression in mice of two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens, in the mammary epithelium recapitulates loss of p53 and Rb function and deregulation of PP2A-controlled mitogenic pathways in human breast cancer. In primiparous mice, WAP-promoter driven expression of SV40 proteins induces well and poorly differentiated mammary adenocarcinomas. We performed a correlative aCGH and gene expression analysis of 25 monofocal tumors, representing four histopathological grades, to explore the molecular traits of SV40-induced mammary tumors and to emphasize the relevance of this tumor model for human breast tumorigenesis.
Publication Title
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The biology of chronic myeloid leukemia (CML)-stem cells is still incompletely understood. Therefore, we previously developed an inducible transgenic mouse model in which stem cell targeted induction of BCR-ABL expression leads to chronic phase CML-like disease. Here, we now demonstrate that the disease is transplantable using BCR-ABL positive LSK cells (lin-Sca-1+c-kit+). Interestingly, the phenotype is enhanced when unfractionated bone marrow (BM) cells are transplanted. However, neither progenitor cells (lin-Sca-1-c-kit+) nor mature granulocytes (CD11b+Gr-1+), or potential stem cell niche cells were able to transmit the disease or alter the phenotype. The phenotype was largely independent of BCR ABL priming prior to transplant. However, BCR-ABL abrogated the potential of LSK cells to induce full blown disease in secondary recipients. Subsequently, we found that BCR-ABL increased the fraction of multipotent progenitor cells (MPP) at the expense of long term HSC (LT-HSC) in the BM. Microarray analyses of LSK cells revealed that BCR-ABL alters the expression of genes involved in proliferation, survival, and hematopoietic development. Our results suggest that BCR-ABL induces differentiation of LT-HSC and decreases their self renewal capacity. Furthermore, reversion of BCR-ABL eradicates mature cells while leukemic stem cells persist, giving rise to relapsed CML upon re-induction of BCR-ABL.
Publication Title
BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells.
Sample Metadata Fields
Specimen part
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