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GSE88935
Mus musculus
6 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Differentiation of hematopoietic stem cells (HSCs) is regulated by a concert of different transcription factors (TFs). A disturbed function of TFs can be the basis of (pre)malignancies such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Growth Factor Independence 1b (Gfi1b) is a repressing TF with a key role in quiescence of HSCs and emergence and maturation of erythrocytes and platelets. Here, we show that low expression of GFI1B in blast cells is associated with inferior prognosis of MDS and AML patients. Using mouse models with either reduced expression or conditional deletion of Gfi1b, crossed with a mouse model reflecting human MDS or AML, we demonstrate that AML development was accelerated with heterozygous loss of Gfi1b, and latency was further decreased when Gfi1b was conditionally deleted. Loss of Gfi1b significantly enhanced stemness of leukemic cells with upregulation of genes fundamentally involved in leukemia development. On a molecular level, we found that loss of Gfi1b not only increased the levels of reactive oxygen species (ROS) but also induced gene expression changes of key AML pathways such as the p38/AKT pathway. These results demonstrate that Gfi1b functions as an oncosuppressor in MDS/AML development.
Publication Title
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
Description
Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of beige cells from murine white fat depots.
Publication Title
Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Description
G1ME cells are GATA1-deficient murine bipotential megakaryocyte/erythrocyte progenitor cells derived from Gata1-negative murine ES cells. In order to assess the impact of GATA1 on gene regulation and cell differentiation, an expression construct was used to transiently produce high levels of GATA1. Cells transduced with this construct or a vector control were harvested at 18 and 42 hours, and gene expression was analyzed using Affymetrix MOE430 version 2 arrays.
Publication Title
Graded repression of PU.1/Sfpi1 gene transcription by GATA factors regulates hematopoietic cell fate.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Rod and cone photoreceptors in mammalian retina are generated from common pool(s) of neuroepithelial progenitors. NRL, CRX and NR2E3 are key transcriptional regulators that control photoreceptor differentiation. Mutations in NR2E3, a rod-specific orphan nuclear receptor, lead to loss of rods, increased density of S-cones, and supernormal S-cone-mediated vision in humans. To better understand its in vivo function, NR2E3 was expressed ectopically in the Nrl-/- retina, where post-mitotic precursors fated to be rods develop into functional S-cones similar to the human NR2E3 disease. Expression of NR2E3 in the Nrl-/- retina completely suppressed cone differentiation and resulted in morphologically rod-like photoreceptors, which were not functional. Gene profiling of FACS-purified photoreceptors confirmed the role of NR2E3 as a strong suppressor of cone genes and an activator of a subset of rod genes (including rhodopsin) in vivo. Ectopic expression of NR2E3 in cone precursors and differentiating S-cones of wild type retina also generates rod-like cells. The dual regulatory function of NR2E3 is not dependent upon the presence of NRL and/or CRX, but on the timing and level of its expression. Our studies reveal a critical role of NR2E3 in establishing functional specificity of post-mitotic photoreceptor precursors during retinal neurogenesis.
Publication Title
In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
microRNA miR-144/451 is highly expressed during erythropoiesis. We deleted the miR-144/451 gene locus in mice and compared the transcriptomes of miR-144/451-null bone marrow erythroid precursors to stage-matched wild-type control cells.
Publication Title
miR-451 protects against erythroid oxidant stress by repressing 14-3-3zeta.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Purpose: To investigate the gene regulatory networks during photoreceptor differentiation.
Publication Title
Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Endothelial inflammation contributes to the pathogenesis of numerous human diseases; however, the role of tumor endothelial inflammation in the growth of experimental tumors and its influence on the prognosis of human cancers is less understood. TNF-, an important mediator of tumor stromal inflammation, is known to target the tumor vasculature. In this study, we demonstrate that B16-F1 melanomas grew more rapidly in C57BL/6 wild-type (WT) mice than in syngeneic mice with germline deletions of both TNF- receptors (KO). This enhanced tumor growth was associated with increased COX2 inflammatory expression in WT tumor endothelium compared to endothelium in KO mice. We purified endothelial cells from WT and KO tumors and characterized dysregulated gene expression, which ultimately formed the basis of a 6-gene Inflammation-Related Endothelial-derived Gene (IREG) signature. This inflammatory signature expressed in WT tumor endothelial cells was trained in human cancer datasets and predicted a poor clinical outcome in breast cancer, colon cancer, lung cancer and glioma. Consistent with this observation, conditioned media from human endothelial cells treated with pro-inflammatory cytokines (TNF- and interferons) accelerated the growth of human colon and breast tumors in immune-deprived mice as compared with conditioned media from untreated endothelial cells. These findings demonstrate that activation of endothelial inflammatory pathways contributes to tumor growth and progression in diverse human cancers.
Publication Title
Tumor endothelial inflammation predicts clinical outcome in diverse human cancers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 4 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MEK inhibition induces MYOG and remodels super-enhancers in RAS-driven rhabdomyosarcoma.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Description
C2C12 mouse myoblasts expressing RAS mutants identified in human tumors fail to differentiate in low serum media.
Publication Title
MEK inhibition induces MYOG and remodels super-enhancers in RAS-driven rhabdomyosarcoma.
Sample Metadata Fields
No sample metadata fields
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