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GSE53482
Homo sapiens
146 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
Ph-negative myeloproliferative neoplasms (MPNs) are characterized by many somatic mutations which have already been shown useful in the prognostic assessment of MPN patients. Moreover, aberrant microRNA (miRNA) expression seems to add to the molecular complexity of MPNs, as specific miRNA signatures capable of discriminating MPN cells from those of normal donors were previously reported. In order to have a comprehensive picture of miRNA deregulation and its relationship with differential gene expression in primary myelofibrosis (PMF) cells, we obtained gene- (GEP) and miRNA expression profiles (miEP) of CD34+ cells from 31 healthy donors and 42 PMF patients using Affymetrix technology (HG-U219 and miRNA 2.0 arrays). Differentially expressed genes (DEG) and miRNAs (DEM) were sorted out by means of Partek Genomic Suite vs 6.6. Since each miRNA can target many mRNAs while a single mRNA can be targeted by multiple miRNAs, we performed Integrative Analysis (IA) by means of Ingenuity Pathway Analysis (IPA) to untangle this combinatorial complexity. In particular, IPA points out DEM-DEG pairs among experimentally validated interactions from TarBase, miRecords and Ingenuity Expert Findings as well as predicted microRNA-mRNA interactions from TargetScan. IPA microRNA Target Filter was then employed to select only the DEM-DEG pairs showing an anti-correlated expression pattern and to build regulatory networks. Finally, 3'UTR luciferase reporter assays were performed to validate IPA predicted miRNA-mRNA interactions.
Publication Title
miRNA-mRNA integrative analysis in primary myelofibrosis CD34+ cells: role of miR-155/JARID2 axis in abnormal megakaryopoiesis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
JARID2 is a chromatin remodeler, member of the Jumonji family of transcription factor genes that belongs to the polycomb repressive complex 2 (PRC2) (Peng JC et al. Cell 2009) and is frequently deleted in leukemic transformation of chronic myeloid malignancies (Puda A et al. Am J Hematol. 2012). In this work, we compared gene expression profile (GEP) of CD34+ cells from Primary Myelofibrosis (PMF) patients with healthy donors and we found JARID2 among downregulated genes. In addition, integrative analysis of gene and miRNA profiles highlighted JARID2 as a shared target of several miRNAs aberrantly expressed in PMF CD34+ cells. Since the role of JARID2 in normal and malignant hematopoiesis has never been investigated, we performed JARID2 silencing experiments on normal Cord Blood (CB) CD34+ cells to evaluate its involvement in proliferation and commitment. Therefore, CD34+ cells were transfected with a mixture of 3 Silencer Select siRNAs targeting JARID2 mRNA and with a non-targeting siRNA as control (NegCTR). The expression level of JARID2 in control samples and JARID2-siRNA cells was assessed by QRT-PCR at 24h (RQ 0,2 SEM 0,036, p <.001) and 48h (RQ 0,32 SEM 0,026, p<.001) after the last nucleofection.
Publication Title
miRNA-mRNA integrative analysis in primary myelofibrosis CD34+ cells: role of miR-155/JARID2 axis in abnormal megakaryopoiesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 130 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
CALR mutational status identifies different disease subtypes of essential thrombocythemia showing distinct expression profiles.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Polycythemia vera (PV) and essential thrombocythemia (ET) are Philadelphia-negative myeloproliferative neoplasms (MPNs) characterized by erythrocytosis and thrombocytosis, respectively. Approximately 95% of PV and 5070% of ET patients harbour the V617F mutation in the exon 14 of JAK2 gene, while about 20-30% of ET patients carry CALRins5 or CALRdel52 mutations. These ET CARL-mutated subjects show higher platelet count and lower thrombotic risk compared to JAK2-mutated patients. Here we showed that CALR-mutated and JAK2V617F-positive CD34+ cells have different gene and miRNA expression profiles. Indeed, we highlighted several pathways differentially activated between JAK2V617F- and CALR-mutated progenitors, i.e. mTOR, MAPK/PI3K and MYC pathways. Furthermore, we unveiled that the expression of several genes involved in DNA repair, chromatin remodelling, splicing and chromatid cohesion are decreased in CALR-mutated cells. According to the low risk of thrombosis in CALR-mutated patients, we also found the down-regulation of several genes involved in thrombin signalling and platelet activation. As a whole, these data support the model in which CALR-mutated ET could be considered as a distinct disease entity from JAK2V617F-positive MPNs and may provide the molecular basis supporting the different clinical features of these patients.
Publication Title
CALR mutational status identifies different disease subtypes of essential thrombocythemia showing distinct expression profiles.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To investigate the time-dependent and coordinated sequence of inflammation-related events, and the dynamic features of macrophage polarisation/activation, we build and validated an in vitro model based on primary human monocytes
Publication Title
Transcriptomic profiling of the development of the inflammatory response in human monocytes in vitro.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The Japanese Serous Ovarian Cancer Study Group
Publication Title
High-risk ovarian cancer based on 126-gene expression signature is uniquely characterized by downregulation of antigen presentation pathway.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Hydrolyzed wheat proteins (HWPs) contained in cosmetics have occasionally caused immediate-type hypersensitivity following repeated skin exposure. Although the Cosmetic Ingredient Review Expert Panel concluded that <3,500 Da HWP is safe for use in cosmetics, it remains biologically unknown how allergenic HWPs evoke immediate-type allergy percutaneously. Keratinocyte-derived thymic stromal lymphopoietin (TSLP) induces type 2 immune responses, which play an essential role in the pathogenesis of immediate-type allergy. Previously, we demonstrated that protein allergens in cultured human keratinocytes strongly induced long-form TSLP (loTSLP) transcription. However loTSLP-regulating signaling by HWP is poorly understood.
Publication Title
An acid-hydrolyzed wheat protein activates the inflammatory and NF-κB pathways leading to long TSLP transcription in human keratinocytes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expressions relate to the pathogenesis of periodontitis and have a crucial role in local tissue destruction and susceptibility to the disease. The aims of the present study were to explore comprehensive gene expressions/transcriptomes in periodontitis-affected gingival tissues, and to identify specific biological processes.
Publication Title
Altered gene expression in leukocyte transendothelial migration and cell communication pathways in periodontitis-affected gingival tissues.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MED1 (Mediator complex subunit 1) is expressed by human epidermal keratinocytes and functions as a coactivator of several transcription factors. To elucidate the role of MED1 in keratinocytes, we established keratinocyte-specific MED1-null (MED1epi-/-) mice using the K5Cre-LoxP system.
Publication Title
Roles of MED1 in quiescence of hair follicle stem cells and maintenance of normal hair cycling.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Gene expression was examined in granulosa cells and oocytes in various stage of follicle and in vitro grown oocytes and granulosa cells complexes in sus scrofa.
Publication Title
Gene expression patterns in granulosa cells and oocytes at various stages of follicle development as well as in in vitro grown oocyte-and-granulosa cell complexes.
Sample Metadata Fields
Specimen part
View Samples