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Intrathymic origins of T-ALL

ABSTRACT: Leukemia cells are considered developmentally 'frozen', and their phenotype is thought to reflect their stage of origin. To gain insights into the cell population from which T-ALL arises, we compared by global gene expression profiling T-ALL samples (n = 10) to different stages of T cell development, following the order from early thymic progenitor (ETP), to triple negative (TN) TN2, to TN3, to TN4, to immature single positive (ISP), to double positive (DP) thymocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE56416 | GEO | 2014/05/16

SECONDARY ACCESSION(S): PRJNA243281

REPOSITORIES: GEO

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Intrathymic origins of T-ALL

Project description:Leukemia cells are considered developmentally 'frozen', and their phenotype is thought to reflect their stage of origin. To gain insights into the cell population from which T-ALL arises, we compared by global gene expression profiling T-ALL samples (n = 10) to different stages of T cell development, following the order from early thymic progenitor (ETP), to triple negative (TN) TN2, to TN3, to TN4, to immature single positive (ISP), to double positive (DP) thymocytes. Comparison of global gene expression between T-ALL samples and various stages of T cell development.

2014-05-16 | E-GEOD-56416 | biostudies-arrayexpress

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.

2020-12-17 | GSE156070 | GEO

T-cell development

Project description:T cells develop from progenitors that migrate from the bone marrow into the thymus. Thymocytes are subdivided roughly as being double negative (DN), double positive (DP), or single positive (SP), based on the expression of the CD4 and CD8 coreceptors. The DN stage is heterogeneous and can be subdivided into four distinct subsets in mice based on the expression of CD44 and CD25. In human, three distinct DN stages can be recognized: a CD34+CD38−CD1a− stage that represents the most immature thymic subset and the consecutive CD34+CD38+CD1a− and CD34+CD38+CD1a+ stages. Human DN thymocytes mature via an immature single positive (ISP CD4+) and a DP stage into CD4+ or CD8+ SP T cells that express functional T cell receptors (TCR) and that exit the thymus. In this study, gene expression was measured in each of these nine stages.

2010-06-28 | GSE22601 | GEO

Paxbp1 is indispensable for the survival of CD4 and CD8 double-positive thymocytes

Project description:The lifespan of double-positive (DP) thymocytes is critical for intrathymic development and shaping the peripheral T cell repertoire. However, the molecular mechanisms that control DP thymocyte survival remain poorly understood. Paxbp1 is a conserved nuclear protein that has been reported to play important roles in cell growth and development. Its high expression in T cells suggests a possible role in T cell development. Here, we observed that deletion of Paxbp1 resulted in thymic atrophy in mice lacking Paxbp1 in the early stages of T cell development. Conditional loss of Paxbp1 resulted in fewer CD4+CD8+ DP T cells, CD4 and CD8 single positive (SP) T cells in the thymus, and fewer T cells in the periphery. Meanwhile, Paxbp1 deficiency had limited effects on the CD4-CD8- double negative (DN) or immature single-positive (ISP) cell populations. Instead, we observed a significant increase in the susceptibility of Paxbp1-deficient DP thymocytes to apoptosis. Consistent with this, RNA-Seq analysis revealed a significant enrichment of the apoptotic pathway within differentially expressed genes in Paxbp1-deficient DP cells compared to control DP cells. Together, our results suggest a new function for Paxbp1, which is an important mediator of DP thymocyte survival and critical for proper thymic development.

2023-06-14 | GSE233211 | GEO

Transcriptional Changes during T cell development following conditional loss of Bcl6

Project description:In this study we investigated the changes during T cell development in Rag knockout Bcl6 conditional knockout E16.5 thymi compared to Control E16.5 thymi. We measured the transcription changes by RNA seq in three different populations including CD25+, CD8+CD4- (ISP) and CD8+CD4+ (DP) thymocytes.

2020-09-24 | GSE152944 | GEO

The Zmiz1-Notch1 interaction induces Myc expression to drive steady state and stress thymopoiesis [ETP and DN3]

Project description:Notch1 signaling ramps up to very high levels in order to drive CD4-CD8- double-negative (DN) thymocytes to the CD4+CD8+ double-positive (DP) stage. During this important phase of T-cell development, which is known as the DN-DP transition, it is unclear whether the Notch1 complex simply strengthens its signal output as an isolated unit or recruits cofactors to amplify its signals. We previously showed that the PIAS-like coactivator Zmiz1 is a direct and context-dependent cofactor of Notch1 in T-cell leukemia. Using conditional knockout mouse models, we show that like inactivation of Notch, inactivation of Zmiz1 impaired the DN-DP transition under steady state and stress conditions. To determine mechanism, we performed RNA-Seq on sorted early T-lineage progenitor (ETP) and DN3 cells that were deprived of Zmiz1 signals either acutely (DeltaTamCre) or chronically (DeltaMxCre). To differentiate Notch1-independent from Notch1-dependent target genes, we also performed RNA-Seq on ETP and DN3 cells that were deprived of Notch1 signals using the anti-NRR Notch1 antibody. Our data suggests that Zmiz1 selectively amplifies a subset of Notch1 target genes in DN3 cells, such as Myc. In contrast, Zmiz1 does not have these functions in ETP cells, thus indicating stage-specific roles of Zmiz1.

2018-09-21 | GSE116120 | GEO

Gene Expression of Double Positive LCK:Hdac3 KO 3w old mice

Project description:Analysis of gene expression in double positive (DP) thymoctes from 3w old LCK Hdac3 conditional KO mice. In this data set we sorted GFP double positive (DP) thymocytes from 3w old mice to identify possible signaling and transcripitonal programs that might explain the DP to single positive block in cell maturation

2015-09-29 | GSE73533 | GEO

Analysis of Differentially Expressed Genes in sorted CD4+ CD8+ doubl positive (DP) thymocytes from wild type (WT) and NSRP1CD4Cre (KO) mice

Project description:NSrp70 deficiency (NSRP1f/fCD4Cre) profoundly perturbed the late development of DP thymocytes, leading to a significant reduction of single positive (SP) cells in the thymus and peripheral lymphoid tissues. To gain further insight how NSrp70 controls thymocyte development from DP stage, we performed RNA-seq analysis after sorting DP thymocytes from WT and Nsrp1 cKO mice.

2021-06-15 | GSE168379 | GEO

Analysis of Differentially Expressed Genes in sorted CD69+ double positive (DP) thymocytes from wild type (WT) and NSRP1CD4Cre (KO) mice

Project description:NSrp70 deficiency (NSRP1f/fCD4Cre) profoundly perturbed the late development of DP thymocytes, leading to a significant reduction of single positive (SP) cells in the thymus and peripheral lymphoid tissues. To gain further insight into how NSrp70 controls thymocyte development from CD69+ DP stage, we performed RNA-seq analysis after sorting CD69+ DP thymocytes from WT and Nsrp1 cKO mice.

2020-06-27 | GSE153389 | GEO

Cohesin regulates gene expression through spatial clustering of enhancer elements

Project description:H3K27Ac ChIP-seq in wild type and cohesin-deficient thymocytes Rad21 was deleted in CD4+ CD8+ double positive (DP) thymocytes by crossing a Rad21 floxed allele with a Cd4-driven Cre transgene. DP positive thymocytes were FACS-sorted from control and Rad21-/- littermates, which were then used to perform chromatin immunoprecipitation for histone H3 acetylated on lysine 27 (H3K27Ac).

2015-02-12 | E-GEOD-61428 | biostudies-arrayexpress

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