This SuperSeries is composed of the SubSeries listed below.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesMice were treated with either 100mg/kg baclofen or 0.5% methylcellulose alone by oral gavage for 1 or 5 days.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesMice were dosed with 2-BE (900mg/kg) or vehicle by oral gavage and sacrificied either after 4 hours of a single dose or after 7 days of daily dosing.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesMemory CD8+ P14 cells were generarted through adoptive transfer and infection with LCMV armstrong. Then, early memory (after 30 - 45 days) and late memory (after 8 months) cells were sort purified based on CD62L expression.
Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Site-specific programming of the host epithelial transcriptome by the gut microbiota.
Sex, Specimen part
View SamplesDifferential expression of genes between Arabidopsis WRKY18/40 knock out and wild type plants, after 8 h post inoculation of powdery mildew pathogen.
Transcriptional reprogramming regulated by WRKY18 and WRKY40 facilitates powdery mildew infection of Arabidopsis.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia.
Specimen part
View SamplesBone marrow samples from normal adult male donors were collected into EDTA. Red cells were removed by ammonium chloride lysis. Leukocytes were washed in SM buffer and CD34+ cells were separated from CD34- cells using an AutoMACS device and anti-CD34 immunomagnetic beads (Miltenyi Biotec), according to manufacturers instructions. For mature cell populations, CD34- cells were FACS purified according to the following immunophenotypes, with 7-AAD used to exclude dead cells: Neutrophils: side scatter high CD15+ CD16+. Monocytes: side scatter low-intermediate CD14+ CD16- CD15-. See also Huang et al., 2014.
Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia.
Specimen part
View SamplesGiven the importance of deregulated phosphoinositide (PI) signaling in leukemic hematopoiesis, genes coding for proteins that regulate PI metabolism may have significant and as yet unappreciated roles in leukemia. We performed a targeted knockdown screen of PI modulator genes in human AML cells and identified candidates required to sustain proliferation or prevent apoptosis. One of these, the lipid kinase phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP4K2A) regulates cellular levels of phosphatidylinositol-5-phosphate (PtsIns5P) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). We found PIP4K2A to be essential for the clonogenic and leukemia-initiating potential of human AML cells, and for the clonogenic potential of murine MLL-AF9 AML cells. Importantly, PIP4K2A is also required for the clonogenic potential of primary human AML cells. Its knockdown results in accumulation of the cyclin-dependent kinase inhibitors CDKN1A and CDKN1B, G1 cell cycle arrest and apoptosis. Both CDKN1A accumulation and apoptosis were partially dependent upon activation of the mTOR pathway. Critically, however, PIP4K2A knockdown in normal hematopoietic stem and progenitor cells, both murine and human, did not adversely impact either clonogenic or multilineage differentiation potential, indicating a selective dependency which we suggest may be the consequence of the regulation of different transcriptional programmes in normal versus malignant cells. Thus, PIP4K2A is a novel candidate therapeutic target in myeloid malignancy.
A targeted knockdown screen of genes coding for phosphoinositide modulators identifies PIP4K2A as required for acute myeloid leukemia cell proliferation and survival.
Specimen part, Time
View SamplesThe Iroquois homeodomain transcription factor gene IRX3 is highly expressed in the developing nervous system, limb buds and heart. In adults, expression levels specify risk of obesity. We now report a significant functional role for IRX3 in human acute leukemia. While transcript levels are very low in normal human bone marrow cell populations, high level IRX3 expression is observed in ~30% of patients with acute myeloid leukemia (AML), ~50% of patients with T-acute lymphoblastic leukemia and ~20% of patients with B-acute lymphoblastic leukemia, typically in association with high levels of HOXA9. Expression of IRX3 alone was sufficient to immortalise murine bone marrow stem and progenitor cells, and induce T- and B-lineage leukemias in vivo with incomplete penetrance. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine bone marrow stem and progenitor cells substantially enhanced the morphologic and phenotypic differentiation block of the resulting AMLs by comparison with Hoxa9-only leukemias, through suppression of a myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 modulates the cellular consequences of HOX gene expression to enhance differentiation block in human AML. Overall design: Murine acute myeloid leukemias - 3 samples from separate mice with AML initiated by HOXA9 and 3 samples from separate mice with AML initiated by HOXA9 and IRX3 coexpression
Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia.
Specimen part, Cell line, Subject
View Samples