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GSE12837
Homo sapiens
24 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Publication Title
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Publication Title
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The molecular etiology of uterine leiomyosarcoma (ULMS) is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS, fibroids, and normal myometrium (NL) to identify clinically relevant molecular subtypes. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods.
Publication Title
Molecular subtypes of uterine leiomyosarcoma and correlation with clinical outcome.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 246 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 93 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The identification of deregulated miRNA in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In the present study, we take virtue of in silico integrative genomics analysis to generate an unprecedented global view of the transcriptional regulatory networks modulated in MM to define microRNAs impacting in regulatory circuits with potential functional and clinical relevance. miRNA and gene expression profiles in two large representative MM datasets, available from retrospective and prospective clinical trials and encompassing a total of 249 patients at diagnosis, were analyzed by means of two robust computational procedure to identify (i) relevant miRNA/transcription factors/target gene circuits in the disease and (ii) highly modulated miRNA-gene networks in those pathways enriched with miRNA-target gene interactions in specific MM subgroups. The analysis reinforced the pivotal role the miRNA cluster miR-99b/let-7e/miR-125a, specifically deregulated in MM patients with t(4;14) translocation, and disentangled its major relationships with transcriptional relevance. Integrated pathway analyses performed on the expression data of the MM patients stratified according to t(4;14) further allowed to define the pathway composed by the interactions that mainly characterize this MM subset and unravel connected pathways with putative role in the tumor biology.
Publication Title
Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The identification of deregulated miRNA in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In the present study, we take virtue of in silico integrative genomics analysis to generate an unprecedented global view of the transcriptional regulatory networks modulated in MM to define microRNAs impacting in regulatory circuits with potential functional and clinical relevance. miRNA and gene expression profiles in two large representative MM datasets, available from retrospective and prospective clinical trials and encompassing a total of 249 patients at diagnosis, were analyzed by means of two robust computational procedure to identify (i) relevant miRNA/transcription factors/target gene circuits in the disease and (ii) highly modulated miRNA-gene networks in those pathways enriched with miRNA-target gene interactions in specific MM subgroups. The analysis reinforced the pivotal role the miRNA cluster miR-99b/let-7e/miR-125a, specifically deregulated in MM patients with t(4;14) translocation, and disentangled its major relationships with transcriptional relevance. Integrated pathway analyses performed on the expression data of the MM patients stratified according to t(4;14) further allowed to define the pathway composed by the interactions that mainly characterize this MM subset and unravel connected pathways with putative role in the tumor biology.
Publication Title
Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumor growth is associated with a profound alteration of myelopoiesis, leading to recruitment of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs). Immuno-regulatory activity of both tumor-induced and BM-derived MDSCs (by GM-CSF and IL-6 treatment) was entirely dependent on C/EBP transcription factor (TF), a key component of the emergency myelopoiesis triggered by stress and inflammation. We used miR expression analysis to identify miRs which could drive MDSC recruitment/generation/activity by modulating specific TFs and pathway. In particular, we identified a miR signature of 79 miR differentially expressed between not suppressive CD11b+ cells and CD11b+ isolated from tumor mass and spleen of tumor-bearing mice. Moreover on the same samples we profiled gene expression with Affymetrix microarrays to perform an integrated analysis of mirna and gene expression.
Publication Title
miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumor progression is accompanied by an altered myelopoiesis that causes the accumulation of cells inhibiting anti-tumor T lymphocytes. We previously reported that immunosuppressive cells can be generated in vitro from bone marrow cells (BM) after four days GM-CSF and IL-6 treatment. Here, we describe that miR-142-3p down-regulation directs macrophage differentiation and determines the acquisition of their immunosuppressive function in cancer. Enforced miR over-expression impaired monocyte to macrophage transition both in vitro and in vivo. Conversely, forced miR down-regulation promoted the generation of immunosuppressive macrophages even during G-CSF-induced granulocytic differentiation. To identify how miR-142-3p regulates MDSC generation and activity, we analyze the gene expression of BM cultures transfected with either CTRL- or miR 142-3p mimic oligo -transfected before four days GM-CSF and IL-6 treatment.
Publication Title
miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis.
Sample Metadata Fields
Specimen part, Treatment
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