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Lineage-specific function of Engrailed-2 in the progression of chronic myelogenous leukemia to T cell blast crisis

ABSTRACT: Deregulations in transcription factors lead to abnormal development, like in leukaemias, where chromosomal abnormalities either create chimeric TFs or alter the expression of the existing ones. The characterization of the precise functions of the TFs that regulate blood formation is essential to understand how these mechanisms are altered in malignancies. We have found that Engrailed-2 becomes methylated in the progression to blast crises of T-cell phenotype in chronic myelogenous leukaemia (CML) in human samples. Subsequently we found that En2 is expressed during T-cell development in the mouse and in humans. Engrailed-2 plays an essential role in central nervous system development but it has not been shown to participate in haematopoiesis. Many TFs have been found to play essential functions both in nervous system and blood development, thus making En2 a likely candidate to be involved in haematopoiesis. We have studied haematopoiesis of wild-type vs. En2 knockout mice. To increase our understanding of the possible molecular role(s) of En2 during T cell development, we have compared by microarray analysis the gene expression patterns of En2-/- versus WT sorted DP thymocytes and also CD8+ splenocytes (the two populations in which we had detected En2 expression). Comparisson of global gene xpression profiling between A) CD4+CD8+ lymphocytes isolated from thymus of WT vs. ENK KO mice; and B) CD8+ lymphocytes isolated from spleens of WT vs. ENK KO mice

ORGANISM(S): Mus musculus

SUBMITTER: Victor Segura

PROVIDER: E-GEOD-47612 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Lineage-specific function of Engrailed-2 in the progression of chronic myelogenous leukemia to T cell blast crisis

Project description:Deregulations in transcription factors lead to abnormal development, like in leukaemias, where chromosomal abnormalities either create chimeric TFs or alter the expression of the existing ones. The characterization of the precise functions of the TFs that regulate blood formation is essential to understand how these mechanisms are altered in malignancies. We have found that Engrailed-2 becomes methylated in the progression to blast crises of T-cell phenotype in chronic myelogenous leukaemia (CML) in human samples. Subsequently we found that En2 is expressed during T-cell development in the mouse and in humans. Engrailed-2 plays an essential role in central nervous system development but it has not been shown to participate in haematopoiesis. Many TFs have been found to play essential functions both in nervous system and blood development, thus making En2 a likely candidate to be involved in haematopoiesis. We have studied haematopoiesis of wild-type vs. En2 knockout mice. To increase our understanding of the possible molecular role(s) of En2 during T cell development, we have compared by microarray analysis the gene expression patterns of En2-/- versus WT sorted DP thymocytes and also CD8+ splenocytes (the two populations in which we had detected En2 expression).

2016-05-30 | GSE47612 | GEO

Role of engrailed 2 (EN2) in esophageal squamous cell carcinoma

Project description:A number of homeobox genes have been found to be implicated in the development of various cancers. Here, we investigated the role of engrailed 2 (EN2), a member of the homeobox gene superfamily, in esophageal squamous cell carcinoma

2020-02-04 | GSE136331 | GEO

gene expression profiling

2023-12-31 | GSE228854 | GEO

Engrailed homeoprotein protects mesencephalic dopaminergic neurons from oxidative stress

Project description:Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks and protects dopaminergic neurons against apoptosis. RNA-seq data for differentially expressed genes in the SNpc of En1+/- mice, En2 infused mice and 6-OHDA/En2 injection experiments.

2015-09-24 | E-GEOD-72321 | biostudies-arrayexpress

Gene expression analysis of Akt2 deficient murine naive CD4 T cells cultured in Th17-polarizing conditions for 36 hours

Project description:Akt1 and Akt2, isoforms of the serine threonine kinase Akt, are essential for T cell development. However, their role in peripheral T cell differentiation remains undefined. Using mice with germline deletions of either Akt1 or Akt2, we found that both isoforms are important for Th17 differentiation, although Akt2 loss had a greater impact than Akt1. To better understand the consequences of Akt2 deficiency in the setting of in vitro Th17 differentiation, we used microarray analysis to compare the transcriptional landscape of Akt2â/â and WT cells that had been cultured in Th17 polarizing conditions for 36 hours.

2016-07-03 | E-MTAB-4062 | biostudies-arrayexpress

A long noncoding RNA regulates sister chromatid cohesion [microarray]

Project description:Long noncoding RNAs (lncRNAs) have appeared to be involved in the most diverse cellular processes through multiple mechanisms. Here we describe a previously uncharacterized human lncRNA, CONCR (cohesion regulator noncoding RNA), transcriptionally activated by MYC, which is upregulated in multiple cancer types. The expression of CONCR is cell cycle-regulated, and it is required for cell cycle progression and DNA replication. Moreover, cells depleted of CONCR show severe defects in sister chromatid cohesion, suggesting an essential role for CONCR in cohesion establishment during cell division. CONCR interacts with and regulates the activity of DDX11, a DNA-dependent ATPase and helicase involved in DNA replication. These findings suggest a novel mechanism of action for CONCR in the modulation of DDX11 enzymatic activity, unveiling the direct involvement of a lncRNA in the establishment of sister chromatid cohesion. Characterization of the function of the long noncoding RNA CONCR. A549 were transfected with a control siRNA or with a combination of two siRNAs targeting CONCR. Three independent siRNA-mediated knockdowns (siRNA CONCR REP1, 2 and 3) and controls (siRNA Control REP1, 2 and 3) were used for the analysis.

2016-08-03 | E-GEOD-81599 | biostudies-arrayexpress

Role of engrailed 2 (EN2) in esophageal squamous cell carcinoma

Project description:Role of engrailed 2 (EN2) in esophageal squamous cell carcinoma

| PRJNA562267 | ENA

LOXL2 dependent genes in RA induced mES differentiation

Project description:Our results indicate that oxidation of TAF10 by LOXL2 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. Since TFIID complex is crucial for the expression of Nanog, Klf4, Sox2 and Oct4 and for maintaining the pluripotent state of embryonic stem cells, TAF10 oxidation by LOXL2 leads to inactivation of the pluripotency genes and a loss of pluripotent capacity in embryonic stem cells. Moreover, in vivo results demonstrate an essential role of LOXL2 in neural differentiation during zebrafish development: in the absence of LOXL2 the neural progenitor gene Sox2 is aberrantly overexpressed and neural differentiation is impaired. 12 samples were analyzed: mES transduced with control shRNA (n=3); mES transduced with LOXL2 shRNA (n=3), ES transduced with control shRNA and treated with RA (n=3); ES transduced with LOXL2 shRNA and treated with RA (n=3)

2015-12-21 | E-GEOD-65675 | biostudies-arrayexpress

Microarray data of foetal liver Lin- cKit+ cells obtained from Fh1-deficient and control 14.5 dpc mouse embryos

Project description:Haematopoiesis-specific Fh1 deletion causes lethal foetal liver haematopoietic defects. To understand the impact of Fh1 deletion on the transcriptome of foetal liver Lin- c-Kit+ cells we preformed microarray analysis. To conditionally delete Fh1 in the foetal liver we used the Vav-iCre recombinase and a Fh1 flox allele. Foetal livers were dissected and used to generate a single cell suspension. Lin- c-Kit+ cells were FACS sorted and lysed for total RNA preparation. We collected samples from 4 experimental animals (Fh1 fl/fl; Vav-iCre/+) and 3 control animals (Fh1 fl/fl).

2017-02-08 | E-MTAB-5425 | biostudies-arrayexpress

mRNA profile of CD8 T cells from chronic HBV patients

Project description:The low frequency of HBV-specific CD8+ T cells in the peripheral blood of CHB patients has limited studies of the mechanisms underlying HBV-induced T cell exhaustion. Similar to the expansion defect displayed in HBV-specific CD8+ T cells, TCR-induced proliferation of global CD8+ T cells is impaired in a fraction of chronic HBV (CHB) patients. Thus, examining the molecular regulation of global CD8+ T cell function in CHB patients may provide insight into the exhaustion of HBV-specific CD8+ T cells. We used microarrays to detail the global programme of gene expression of CD8 T cells from CHB patients who have not received anti-viral treatment. Fifteen milliliters of blood was drawn from eachof three CHB patients and three healthy donors. PBMCs were enriched using Ficoll, and CD8+ T cells were purified using positive selection beads to a purity of >95% (Miltenyi Biotec, Auburn, CA). Total RNA was extracted using a mirVana isolation kit (Life Technologies, Carlsbad, CA).

2016-07-01 | E-GEOD-51489 | biostudies-arrayexpress

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