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SRP124824
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2500
Description
Chromosomal translocation t(8;21) (q22;q22) leading to generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is a cytogenetic abnormality observed in about 10% of acute myelogenous leukemia (AML). To uncover somatic mutations that cooperate with t(8;21)-driven leukemia, we performed targeted and whole exome sequencing of newly-diagnosed and relapsed AML samples. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this subtype of AML. To investigate in-depth the role of ASXL2 in normal and malignant hematopoiesis, we utilized a mouse model of ASXL2 deficiency. Loss of ASXL2 caused progressive hematopoietic defects characterized by myeloid cell expansion, splenomegaly, extramedullary hematopoiesis and poor reconstitution ability in transplantation models. A parallel analysis of young and >1-year old Asxl2-deficient mice revealed age-dependent changes in the hematopoietic compartment leading to perturbations affecting not only myeloid and erythroid differentiation but also maturation of lymphoid cells. Our studies also suggest that expression of truncated ASXL2 protein confers proliferative advantage to mouse myeloid progenitors. Overall, these findings establish a critical role of ASXL2 in maintaining steady state hematopoiesis and provide insights into how its loss/mutation primes leukemic growth of myeloid cells. Overall design: Bone marrow derived LSK cells from young (8-12 weeks old) and >1-year old Asxl2 WT and knockout mice were analyzed for gene expression changes.
Publication Title
ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 69 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sporadic early onset colorectal carcinoma (EOCRC) is a growing problem that remains poorly understood. Clinical specificities and mechanisms of tumorigenesis might be relevant to both diagnosis and treatment. In this prospective study, clinicopathological features, genomic and gene expression profiles of sporadic EOCRC were compared to other well defined groups of CRC.
Publication Title
Sporadic early-onset colorectal cancer is a specific sub-type of cancer: a morphological, molecular and genetics study.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 84 Downloadable Samples
- IlluminaHiSeq2000
Description
Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders. Overall design: Total RNA obtained from skin explants taken from psoriatic patients or healthy donors cultured in the presence of AhR agonist or antagonist
Publication Title
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders.
Publication Title
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Differential gene expression was analyzed for FACS sorted Math1::Cre; ROSA-tdTomato from hand dissected cochlear nuclei of wild type and Hoxa2/Hoxb2 mutant mice Overall design: In order to investigate the role of Hoxa2 and Hoxb2 transcription factors in a subset of cells of the cochlear nucleus, we generated double conditional knock-out by crossing the deleter line Math1::Cre crossed with Rosa tdTomato; Hoxa2fl/fl; Hoxb2fl/fl and Rosa tdTomato wild type background. FACS sorted cells from hand dissected cochlear nuclei were than processed and RNA-seq performed (see extract protocol and library construction protocol).
Publication Title
Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Oxidative stress as a result of cigarette smoking is an important etiological factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), a chronic steroid-insensitive inflammatory disease of the airways. The activity of the transcriptional co-repressor Histone deacetylase-2 (HDAC2) is dramatically reduced in COPD and cells exposed to oxidative stress or cigarette smoke. Moreover, curcumin (diferuloylmethane), a dietary polyphenol, at concentrations upto 1uM specifically restores cigarette smoke extract (CSE)- or oxidative stress- impaired HDAC2 activity. The aim of this study was to therefore identify any links through those gene sets that are affected by oxidative stress and subsequent treatment with curcumin in order to determine whether or not this could explain the impact of curcumin on restoration of oxidant impaired HDAC2 transcriptional co-repressor activity.
Publication Title
Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 3000
Description
Keratinocytes isolated from one healthy donor were stimulated in triplicate for 24h with IL-36a, IL-36ß or IL-36? Overall design: Gene expression profile of IL-36 stimulated keratinocytes
Publication Title
An analysis of IL-36 signature genes and individuals with <i>IL1RL2</i> knockout mutations validates IL-36 as a psoriasis therapeutic target.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Case report of a twin pair with concordant JMML, but with a different disease course predicted by gene expression profiling
Publication Title
Different outcomes of allogeneic hematopoietic stem cell transplant in a pair of twins affected by juvenile myelomonocytic leukemia.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We retrospectively analyzed AML patients enrolled in the AIEOP since 2000, 42 patients with 11q23 rearrangement were analyzed by gene expression profile
Publication Title
MLL partner genes drive distinct gene expression profiles and genomic alterations in pediatric acute myeloid leukemia: an AIEOP study.
Sample Metadata Fields
Disease, Disease stage
View Samples