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GSE39991
Homo sapiens
36 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
The post-transcriptional control of mRNA stability plays a critical role in numerous biological functions, including the immune response, cell cycle regulation and DNA damage response. HNRNPA0, which encodes an RNA-binding protein shown to regulate transcript stability via binding to the AU-rich elements (AREs) of mRNAs, is located within the commonly deleted segment of 5q31.2 in therapy-related myeloid neoplasms (t-MNs) with a del(5q). We hypothesized that loss of HNRNPA0 leads to alterations in hematopoietic differentiation due to changes in the expression of its target AU-rich transcripts. Using RNAi interference to model Hnrnpa0 loss in primary murine cells and an experimental cell system, we found that reduced Hnrnpa0 expression leads to a shift from monocytic towards granulocytic differentiation. Microarray-based global expression profiling revealed that Hnrnpa0 knockdown disproportionally impacts ARE-containing transcripts and alters expression of myeloid specification genes. The biological importance of ARE-containing genes in myeloid neoplasms is further supported by changes in gene expression of ARE-mRNAs in t-MN del(5q) patients, predicted by pathway analysis to activate tumor growth. Together, our findings suggest that alterations in ARE-containing genes can positively regulate the cellular proliferation of del(5q) cells and implicate haploinsufficiency of HNRNPA0 as one of the key initiation mutations in the pathogenesis of t-MN.
Publication Title
Knockdown of Hnrnpa0, a del(5q) gene, alters myeloid cell fate in murine cells through regulation of AU-rich transcripts.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase inhibitor lonafarnib and the tyrosine kinase inhibitor nilotinib. This results in an initial large reduction in cell viability of the culture and inhibition of cell proliferation. However, after a number of days, cell death ceases and the culture becomes drug-tolerant, enabling cell division to resume. We used gene expression profiling to analyze changes in the transcriptome of these leukemia cells over a 3-4 week period, taking samples at the start, the point at which most of the leukemia cells had been eradicated while a small percentage survived, and at the end when the cells were proliferating again.
Publication Title
Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Primary pre-B acute lymphoblastic (ALL) cells do not proliferate long-term ex vivo without the presence of stromal support. We developed and use an ex vivo co-culture model, consisting of mouse leukemic pre-B Bcr/Abl-expressing ALL cells grown with mitotically inactivated mouse embryonic fibroblasts (MEFs). This system provides a generic type of environmentally-mediated protection to the ALL cells, because when the ALL cells are treated with a moderate dose of a therapeutic drug, drug-resistant ALL cells can be recovered after a 1-2 week period of culture. Some of the factors produced by stromal cells that provide protection to ALL cells have been identified. However, it is unclear if the presence of drug-treated ALL cells affects the stromal fibroblasts. The current study was initiated to examine this using expression profiling on the irradiated MEFs.
Publication Title
Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared differences in fetal and adult T cells by performing whole genome profiling on sort-purified T cells (nave CD4+ and Treg cells) from human fetal specimens (18-22 gestational weeks) and adult specimens (age 25-40 years old). Fetal and Adult Nave CD4+ T cells phenotype: CD3+CD4+CD45RA+CCR7+CD27+, Fetal and Adult CD4+CD25+ Treg phenotype: CD3+CD4+CD25bright
Publication Title
Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human fetal and adult hematopoietic stem cells (HSC) were obtained from fetal liver, fetal bone marrow (BM), and adult BM. These were injected into human fetal thymic implants in SCID-hu Thy/Liv mice (4-6 separate mice per HSC donor) and allowed to mature into single positive CD4+ (SP4) thymocytes over the course of 7-8 weeks. SP4 thymocytes from injected stem cells were subsequently sort-purified from thymic implants and gene expression was performed.
Publication Title
Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Primary human hepatocytes (PHHs) are a liver-specific cell subtype, and we have shown that these cells respond in a unique manner to the introduction of hepatitis C viral RNA (HCV vRNA) derived from different genotypes of the virus.
Publication Title
Transmitted/founder hepatitis C viruses induce cell-type- and genotype-specific differences in innate signaling within the liver.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 43 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Microarray analysis of parity induced gene expression changes in the mammary glands of four strains of rats to identify a common gene signature associated with protection against methylnitrosourea induced mammary tumorigenesis.
Publication Title
Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
Illumina HiSeq 2500
Description
RNAseq of ex vivo CD8 T cell lineages and in vitro differentiated CD8 T cells treated with nanocarriers encapsulating control or Foxo1-3A transcription factor mRNA Overall design: Gene expression in central memory CD8 and in vitro Foxo1-3A nanoparticle treated CD8 were compared to control cells cultured in vitro with eGFP mRNA encapsulating nanoparticles.
Publication Title
Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RNA expression profiling of human iPSC-derived cardiomyocytes in a cardiac hypertrophy model.
Sample Metadata Fields
Specimen part
View Samples