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MiRNA expression in PTEN-deficient premalignant DP thymocytes

ABSTRACT: T cell-specific deletion of PTEN induces premalignancy in CD4+ CD8+ (DP) immature T cells in the thymus, which progresses to the development of mature CD4+ T cell lymphomas in the lymph nodes and spleen. As part of a screen to identify factors that inhibit progression to malignancy, we compared miRNA expression in premalignant PTEN-deficient DP thymocytes versus wild-type controls.

ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens

PROVIDER: GSE56759 | GEO | 2014/04/12

SECONDARY ACCESSION(S): PRJNA244448

REPOSITORIES: GEO

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miRNA expression in PTEN-deficient premalignant DP thymocytes

Project description:T cell-specific deletion of PTEN induces premalignancy in CD4+ CD8+ (DP) immature T cells in the thymus, which progresses to the development of mature CD4+ T cell lymphomas in the lymph nodes and spleen. As part of a screen to identify factors that inhibit progression to malignancy, we compared miRNA expression in premalignant PTEN-deficient DP thymocytes versus wild-type controls. DP thymocytes were collected by cell sorting from three 9-week-old, premalignant T cell-specific PTEN-deficient mice (tPTEN-/-) and three littermate controls. miRNA expression was assessed relative to a reference pool generated from an equal mixture of all samples.

2014-04-12 | E-GEOD-56759 | biostudies-arrayexpress

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scRNAseq in Pten enhancer wild-type or deleted thymocytes, enriched for immature thymocyte stages (CD4-CD3-)

Project description:Single cell suspensions of total thymocytes were obtained from Pten enhancer (PE) wild-type or knockout mice. This single-cell suspension was enriched in CD4-CD3- immature thymocyte progenitor cells. CD4-CD3- enriched thymocytes were then mixed 1:1 with single-cell suspensions from total unenriched thymocytes and subsequntly loaded in a 10x Chromium instrument for single-cell RNAseq analyses. Our results revealed Pten levels are signifcantly decreased in CD4-CD8- double negative (DN) thymocytes, CD8+ intermediate single positive (ISP) thymocytes and CD4+CD8+ double positive (DP) thymocytes in PE knockout mice, compared to PE wild-type mice.

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Project description:To assess the importance of the Wnt pathway during T cell develoment, we generated a mouse line (R26-βcat) in which high levels of active β-catenin are maintained throughout T cell development. Young R26-βcat mice (6-week-old) show a differentiation block at the CD4+CD8+ DP stage. All R26-βcat mice develop T cell leukemias with a DP phenotype at 5-6 months of age. To identify the molecular pathways involved in tumor development, we profiled the global gene expression of transformed and pre-transformed DP cells.

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Expression data from tumoral thymocytes and DP thymocytes expressing an activated form of b-catenin in mouse T cells

Project description:To assess the importance of the Wnt pathway during T cell develoment, we generated a mouse line (R26-M-NM-2cat) in which high levels of active M-NM-2-catenin are maintained throughout T cell development. Young R26-M-NM-2cat mice (6-week-old) show a differentiation block at the CD4+CD8+ DP stage. All R26-M-NM-2cat mice develop T cell leukemias with a DP phenotype at 5-6 months of age. To identify the molecular pathways involved in tumor development, we profiled the global gene expression of transformed and pre-transformed DP cells. Thymocytes from 6-week-old mice (with a normal sized thymus and a polyclonal thymocyte population) were used to define the pre-transformed transcriptome. RNA from control and pre-leukemic R26-M-NM-2cat DP thymocytes as well as R26-M-NM-2cat total tumor cells were extracted and used for transcriptome analysis.

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2014-04-12 | E-GEOD-56714 | biostudies-arrayexpress

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Project description:miRNA expression in PTEN-deficient premalignant DP thymocytes

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RNA Sequencing Analysis of Gene Expression Profiles in WT and CIC-deficient DP Thymocytes

Project description:Purpose : The goal of this study is to compare the gene expression profiles between wild-type (WT) and CIC-deficient DP thymocytes to understand the molecular mechanisms of CIC regulation of T cell development, especially in DP thymocytes. Methods : DP thymocytes (lin-CD4+CD8+TCRlo (Lineage : CD11b, CD11c, CD19, NK1.1, Gr-1, γδTCR, and TER119)) from thymus were sorted by a MoFlo-XDP (Beckman Coulter). Total RNA was extracted using RiboEX (GeneAll) according to the manufacturer's instructions. The library for mRNA sequencing was generated using the TruSeq Stranded Total RNA LT Sample Prep Kit (Illumina) and sequencing was performed with NovaSeq 6000 (Illumina). Results : Trimmed reads were mapped to the mouse reference genome (mm10 RefSeq) with HISAT2, and the transcripts were assembled using StringTie. A total of 482 differentially expressed genes (DEGs; fold change > 2 and P-value < 0.05) were generated using edgeR. The 263 upregulated genes included known CIC target genes such as Etv1, Etv4, Etv5, Spry4, Spred1, Dusp4, and Dusp6. Conclusions : Our study represents the first comparative analysis of DP thymocytes from WT and hematopoietic lineage cell-specific Cic deficient mice. We concluded that CIC deficiency leads to impaired positive and negative selection, and TCR signaling in DP cells. The attenuation of TCR signaling is caused by derepression of CIC target genes involved in dephosphorylation of ERK.

2021-05-06 | GSE173909 | GEO

Effect of c-Myb deficiency on pre-selection DP thymocytes

Project description:Comparing the mRNA expression profiles of c-Myb deficient and c-Myb sufficient Tcra-/- DP thymocytes. Results provide insight into the role of c-Myb in the regulation of survival and differentiation during the pre-selection DP stage where c-Myb expression is abundant during T cell development.

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