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GSE66256
Mus musculus, Homo sapiens
8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Bone 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.
Publication Title
Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Given 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.
Publication Title
A targeted knockdown screen of genes coding for phosphoinositide modulators identifies PIP4K2A as required for acute myeloid leukemia cell proliferation and survival.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 24 Downloadable Samples
NextSeq 500
Description
The 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
Publication Title
Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Beyond the DNA sequence difference between humans and closely related apes, there are large differences in the environments that these species experience. One prominent example for this is diet. The human diet diverges from those of other primates in various aspects, such as having a high calorie and protein content, as well as being cooked. Here, we used a laboratory mouse model to identify gene expression differences related to dietary differences.
Publication Title
Human and chimpanzee gene expression differences replicated in mice fed different diets.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Beyond the DNA sequence difference between humans and closely related apes, there are large differences in the environments that these species experience. One prominent example for this is diet. The human diet diverges from those of other primates in various aspects, such as having a high calorie and protein content, as well as being cooked. Here, we used a laboratory mouse model to identify gene expression differences related to dietary differences.
Publication Title
Human and chimpanzee gene expression differences replicated in mice fed different diets.
Sample Metadata Fields
Sex, Age
View Samples- Macaca mulatta, Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Macaca mulatta, Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression changes determine functional differentiation during development and are associated with functional decline during aging. While developmental changes are tightly regulated, regulation of aging changes is not well established. To assess the regulatory basis of age-related changes and investigate the mechanism of regulatory transition between development and aging, we measured mRNA and microRNA expression patterns in brains (superior frontal gyrus) of humans and rhesus macaques over the entire species lifespan. We find that in both species, developmental and aging changes overlap in the course of lifetime with many changes found at the late age initiating in early childhood.
Publication Title
MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Macaca mulatta, Pan troglodytes, Homo sapiens
- 103 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA-driven developmental remodeling in the brain distinguishes humans from other primates.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Macaca mulatta, Pan troglodytes, Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We investigated molecular changes during human, chimpanzee, and rhesus macaque postnatal brain development at the transcriptome, proteome, and metabolome levels in two brain regions: the prefrontal cortex (PFC) that is involved in several human-specific cognitive processes, and the cerebellar cortex (CBC) that may be functionally more conserved. We find a nearly three-fold excess of human-specific gene expression changes in PFC compared to CBC. The most prominent human-specific mRNA expression pattern in the PFC is a developmental delay of approximately 5 years in the expression of genes associated with learning and memory, such as synaptic transmission and long-term potentiation. This pattern is supported by correlated changes in concentrations of proteins and the respective neurotransmitters and its magnitude is beyond the shift expected from the life-histories of the species. Mechanistically, it might be driven by change in timing of expression of four or more transcription factors. We speculate that delayed synaptic maturation in PFC may play a role in the emergence of human-specific cognitive abilities.
Publication Title
MicroRNA-driven developmental remodeling in the brain distinguishes humans from other primates.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples