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Gene expression profiling of the Se-Ax cell line following E2A reconstitution

ABSTRACT: The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the proto-oncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells following restoration of E2A expression, we identify a number of E2A-regulated genes that interfere with oncogenic signaling pathways including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE21730 | GEO | 2011/07/07

SECONDARY ACCESSION(S): PRJNA129381

REPOSITORIES: GEO

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Gene expression profiling of the Se-Ax cell line following E2A reconstitution

Project description:The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the proto-oncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells following restoration of E2A expression, we identify a number of E2A-regulated genes that interfere with oncogenic signaling pathways including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity. The E2A-deficient Sézary cell line Seax was transiently transfected with the E2A-expression constructs E47myc (a myc-tagged E47 construct) or E47-forced dimer (a construct coding for two covalently linked E47 molecules), respectively. Every experiment was performed as two replicates accompanied by control transfections with a Mock plasmid.

2011-07-07 | E-GEOD-21730 | biostudies-arrayexpress

Comparative genomic hybridization of 20 patients with Sézary syndrome

2011-07-07 | GSE19000 | GEO

Transcription profiling of human granulocytes and CD3+ T lymphocytes from patients with Sazary syndrome

Project description:This SuperSeries is composed of the following subset Series:; GSE17595: Affymetrix SNP array data for Sézary Syndrome (SS) samples; GSE17601: Affymetrix Gene Expression array data for Sézary Syndrome (SS) samples Experiment Overall Design: Refer to individual Series

2009-10-10 | E-GEOD-17602 | biostudies-arrayexpress

RNA-sequencing of E2a-deficient or E2a and Lef1-deficient leukemia cell lines

Project description:We compared the transcriptome of leukemia cell lines generated from 7 E2a-/- and 8 E2a-/-Lef1f/fLckCre+ mice

2021-10-25 | GSE186420 | GEO

Deciphering Tumor Cell Evolution in Cutaneous T-Cell Lymphomas: Distinct Differentiation Trajectories in Mycosis Fungoides and Sézary Syndrome

Project description:Cutaneous T-cell lymphomas are a heterogeneous group of neoplasms originating in the skin, with mycosis fungoides (MF) and Sézary syndrome (SS) representing the most common variants. The cellular origin of cutaneous lymphomas has remained controversial due to their immense phenotypic heterogeneity that obfuscates lineage reconstruction based on classical surface biomarkers. To overcome this heterogeneity and reconstruct the differentiation trajectory of malignant cells in MF and SS, T-cell receptor sequencing was performed in parallel with targeted transcriptomics at the single-cell resolution among cutaneous samples in MF and SS. Unsupervised lineage reconstruction showed that Sézary cells exist as a population of CD4+ T cells distinct from those in patch, plaque, and tumor MF. Further investigation of malignant cell heterogeneity in SS showed that Sézary cells phenotypically comprised at least three subsets based on differential proliferation potentials and expression of exhaustion markers. A Th1 polarized cell type, intermediate cell type, and exhausted Th2 polarized cell type were identified, with Th1 and Th2 polarized cells displaying divergent proliferation potentials. Collectively, these findings provide evidence to clarify the relationship between MF and SS, and reveal cell subsets in SS that suggest a possible mechanism for therapeutic resistance.

2022-12-31 | GSE192836 | GEO

Transcriptome profiling of wildtype and E2A knockout embryonic stem cells

Project description:Background: E2A, encoded by the TCF3 gene locus, belongs to the E protein transcription factor family, which also includes HEB (TCF12) and E2-2 (TCF4), has been suggested to play an important role in leukemogenesis. However, far less is known about the function of E2A in cell-fate regulation of hESCs. Therefore, further understanding of E2A in self-renewal and differentiation of embryonic stem cells may be influenced. Methods: The mRNA profiles of wildtype and E2A knockout embryonic stem cells were generated by RNA-seq technique, in triplicate for each group, using IIIumina Hiseq 2500. Results: A comprehensive human transcriptome map of wild type and E2A knockout embryonic stem cells was provided. Function enrichment, network characteristics and disease association of the differentially expressed genes were analyzed. Conclusion: The dataset could serve as a baseline resource for investigating the potential effects and mechanism of E2A in embryonic stem cells.

2020-07-16 | GSE154481 | GEO

Allosaccharopolyspora coralli strain:E2A

Project description:Allosaccharopolyspora coralli strain:E2A Genome sequencing

| PRJNA588104 | ENA

HEB and E2A function as SMAD/FOXH1 cofactors

Project description:Nodal signaling, mediated through SMAD transcription factors, is necessary for pluripotency maintenance and endoderm commitment. We have identified a new motif, termed SMAD Complex Associated (SCA) that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. We demonstrate that two bHLH proteins - HEB and E2A - bind the SCA motif at regions overlapping SMAD2/3 and FOXH1. Further, we show that HEB and E2A associate with SMAD2/3 and FOXH1, suggesting they form a complex at critical target regions. This association is biologically important, as E2A is critical for mesendoderm specification, gastrulation, and Nodal signal transduction in Xenopus tropicalis embryos. Taken together, E2A is a novel Nodal signaling cofactor that associates with SMAD2/3 and FOXH1 and is necessary for mesendoderm differentiation.

2011-08-23 | GSE30146 | GEO

Expression data from WT and E2A-deficient murine DN2 cells

Project description:The E2A transcription factors promote the development of thymus-seeding cells but it remains unknown whether these proteins play a role in T lymphocyte lineage specification or commitment. By examining E2A-dependent genes in developing T cells, we will address whether these proteins are involved in these processes. DN2 cells from WT and E2A-deficient murine fetal thymi were FACS sorted. Subsequently RNA was extracted, labelled and hybridized to Affymetrix microarrays. The goal of this study is to investigate E2A-dependent genes in developing T cells

2013-02-01 | E-GEOD-43224 | biostudies-arrayexpress

HEB and E2A function as SMAD/FOXH1 cofactors

2011-08-23 | E-GEOD-30146 | biostudies-arrayexpress

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