Angiogenesis in cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture.
Macrophage-derived tumor necrosis factor-alpha is an early component of the molecular cascade leading to angiogenesis in response to aortic injury.
Sex, Specimen part, Treatment
View SamplesAngiogenesis in collagen gel cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture.
Macrophage-derived tumor necrosis factor-alpha is an early component of the molecular cascade leading to angiogenesis in response to aortic injury.
Sex, Specimen part
View SamplesInhibition of FOXO1 activity in kidney microvascular endothelial cells improves angiogenesis Overall design: Kidney microvascular endothelial cells were serum starved and treated with DMSO control or FOXO1 inhibitor for one hour, then stimulated with VEGF for 30 minutes
Hyperactive FOXO1 results in lack of tip stalk identity and deficient microvascular regeneration during kidney injury.
Specimen part, Treatment, Subject, Time
View SamplesSCL/TAL1, a tissue-specific transcription factor of the basic helix-loop-helix (bHLH) family, and c-Kit, a tyrosine kinase receptor, control hematopoietic stem cell survival and quiescence. Here we report that SCL and c-Kit signaling control a common gene expression signature, of which 19 genes are associated with apoptosis. In vivo, SCL levels are limiting for the clonal expansion of Kit+ multipotent and erythroid progenitors. In addition, increased SCL expression specifically enhances the sensitivity of multipotent and megakaryocyte/erythroid progenitors to Steel factor (KIT ligand), whilst a DNA binding mutant antagonizes KIT function and induces apoptosis in progenitors. We conclude that Scl operates downstream of Kit to support the survival of megakaryocyte/erythroid progenitors. Finally, higher SCL expression upregulates Kit in normal bone marrow cells and increases chimerism after bone marrow transplantation, indicating that Scl is also upstream of Kit. We conclude that Scl and Kit establish a positive feedback loop in multipotent and megakaryocyte/erythroid progenitors.
Genetic interaction between Kit and Scl.
Cell line, Treatment
View SamplesZFP36L2, zinc finger protein 36, C3H type-like 2 (also known as Brf2, Erf2, Tis11D) is a member of the tristetraprolin (TTP; Zfp36) family of tandem CCCH zinc finger proteins that can bind to AU-rich elements (AREs) in the 3'-untranslated region of mRNAs, leading to their deadenylation and subsequent degradation. We have generated Zfp36l2 knockout mice. Knockout mice were born at the expected Mendelian frequency, but within several weeks of birth they died rather suddenly with pallor and frequent intestinal hemorrhage. These mice exhibited pancytopenia, decreased hematopoietic progenitor cells from fetal liver and yolk sac, and ineffective hematopoietic stem cells. Since ZFP26L2 is likely to function as an ARE-containing mRNA destabilizing protein, we were interested in identifying any abnormally stabilized transcripts in fetal livers from the Zfp36l2 knockout mice whose protein product may directly or indirectly affect hematopoietic stem cell function.
Targeted disruption of Zfp36l2, encoding a CCCH tandem zinc finger RNA-binding protein, results in defective hematopoiesis.
Specimen part
View SamplesThe Ets transcription factor, ERG, plays a central role in definitive hematopoiesis and its overexpression in acute myeloid leukemia is associated with a stem cell signature and bad prognosis. However, little is known about the underlying mechanism by which ERG causes leukemia. Therefore we sought to identify ERG targets that participate in development of leukemia by integration of expression arrays and Chromatin immunoprecipitation.
Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia.
No sample metadata fields
View SamplesHere we show that the histone methyltransferase MLL4 (Kmt2d) is required for stem cell activity and an aggressive form of acute myeloid leukemia (AML) harboring the MLL-AF9 oncogene. MLL4 exerts its function by regulating transcriptional programs associated with the anti-oxidant response. Overall design: The role of Mll4 (Kmt2d) in regulating the transcriptome of primary and transformed hematopoietic stem cells was studied.
DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MLL rearrangements impact outcome in HOXA-deregulated T-lineage acute lymphoblastic leukemia: a Children's Oncology Group Study.
Specimen part, Disease
View SamplesThe clinical and cytogenetic features associated with T-cell acute lymphoblastic leukemia (T-ALL) are not predictive of early treatment failure or relapse. We used the Affymetrix U133 Plus 2.0 chip to profile 100 newly diagnosed patients who were treated in the Children's Oncology Group (COG) T-ALL AALL0434. We performed unsupervised hierarchical clustering of 25 HOXA probe sets within the cohort of 100 T-ALL cases. We identified a cluster of 20 cases (20%) characterized by increased expression of HOXA3, 5, 7, 9, and 10. In samples with HOXA9/10 deregulation, the presence of specific molecular lesions were confirmed through a systematic review of cytogenetic databases, FISH and PCR testing, and by RNA sequence analysis. Because MLL and AF10 genes rearrangements (MLL-R, AF10-R) are hallmarks of HOXA-deregulated leukemias, we sought to identify specific genes that are enriched with these genomic abnormalities.
MLL rearrangements impact outcome in HOXA-deregulated T-lineage acute lymphoblastic leukemia: a Children's Oncology Group Study.
Specimen part, Disease
View SamplesTransgenic expression of TLX1 induces T-cell leukemias in mice.
The TLX1 oncogene drives aneuploidy in T cell transformation.
No sample metadata fields
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