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GSE89156
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
Primary Myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. Through a gene expression profile (GEP) study we recently highlighted the upregulationof miR-34a-5p in PMF versus healthy donor (HD) CD34+ hematopoietic progenitor cells (HPCs). To shed some light into the role of miR-34a-5p in PMF pathogenesis, here we unravelled the effects of the overexpression of miR-34a-5p in HPCs forcing its expression in HPCs.
Publication Title
Role of miR-34a-5p in Hematopoietic Progenitor Cells Proliferation and Fate Decision: Novel Insights into the Pathogenesis of Primary Myelofibrosis.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
As recently reported by our group, we performed miRNA and gene expression profiling of CD34+ hematopoietic stem/progenitor cells (HSPCs) isolated from 42 PMF patient samples compared with 31 healthy controls. Integrative analysis of these profiles by means of Ingenuity Pathway Analysis (IPA) allowed the identification of several aberrantly regulated miRNA-mRNA target pairs organized in interaction networks. In particular, our results highlighted the up-regulation of miR-494-3p in CD34+ cells from PMF patients (Norfo R et al, Blood, 2014). Interestingly, among the most upregulated miRNAs, miR-494-3p emerges as being associated to the highest number of downregulated target mRNAs. In order to understand the biological role of miR-494-3p during the hematopoietic commitment and differentiation, we overexpressed this miRNA in cord blood (CB) derived-CD34+ cells. Cells were electroporated with either miR-494-3p miRNA mimic (mimic miR-494) or a negative control mimic (mimic Neg CTR). qRT-PCR confirmed miR-494-3p overexpression 24h and 4 days after transfection (RQ SEM, 512.60 137.37, p<.01, and 20.63 3.03, p<.01, respectively).
Publication Title
miR-494-3p overexpression promotes megakaryocytopoiesis in primary myelofibrosis hematopoietic stem/progenitor cells by targeting SOCS6.
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
- 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- Saccharomyces cerevisiae
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
GATA transcription factors are highly conserved among eukaryotes and play roles in transcription of genes implicated in cancer progression and hematopoiesis. However, although their consensus binding sites have been well defined in vitro, the in vivo selectivity for recognition by GATA factors remains poorly characterized. Using ChIP-Seq, we identified the Dal80 GATA factor targets in yeast. Our data reveal Dal80 binding to a large set of promoters, sometimes independently of GATA sites, correlating with nitrogen- and/or Dal80-sensitive gene expression. Strikingly, Dal80 was also detected across the body of promoter-bound genes, correlating with high expression. Mechanistic single-gene experiments showed that Dal80 spreading across gene bodies requires active transcription. Consistently, Dal80 co-immunoprecipitated with the initiating and post-initiation forms of RNA Polymerase II. Our work suggests that GATA factors could play dual, synergistic roles during transcription initiation and post-initiation steps, promoting efficient remodeling of the gene expression program in response to environmental changes. Overall design: Strand-specific total RNA-Seq analysis in wild-type (WT) and dal80-delta (dal80) cells grown in glutamine- and/or proline-containing medium.
Publication Title
Transcription-dependent spreading of the Dal80 yeast GATA factor across the body of highly expressed genes.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
During early development before gonadal differentiation, sex chromosomes are the main difference between males and females. We examined any genetically driven sex dimorphisms in human pluripotent stem cells focusing on Y chromosome contribution.
Publication Title
Sex-dependent gene expression in human pluripotent stem cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Developmentally synchronized animals were obtained by hypochlorite treatment of gravid adults to release embryos. Synchronized embryos were hatched on NGM plates and grown at 20°C until 48 h after the L4 stage of development. Fluorodeoxyuridine was used to prevent the development of second-generation embryos once animals reached fertile adulthood. For each RNA-seq experiment, populations for odIs77[Pcol-19::UbG76V-GFP] and dop-1(vs100); [Pcol- 19::UbG76V-GFP] were grown simultaneously under the same conditions. Total RNA was isolated from animals using trizol (Invitrogen) combined with Bead Beater lysis in 3 biological replicates, and an mRNA library (single-end, 50-bp reads) was prepared for each sample/replicate using Illumina Truseq with PolyA selection. Overall design: Examination of mRNA levels in adults dop-1 mutants and wild-type animals.
Publication Title
Dopamine signaling promotes the xenobiotic stress response and protein homeostasis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Embryonic fibroblast from C57BL/6 (B6) mice were reprogrammed to EiPS without exogenous DNA integration using an single episomal vector. The EiPS cells and B6 ES cells were then transplanted into B6 mice to form teratomas.
Publication Title
Immunogenicity of induced pluripotent stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples