RNA-seq profiling of thymocytes from wildtype and Lmo2-transgenic mice
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ABSTRACT:
PROVIDER: PRJNA777946 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptional profiling of Lmo2 transgenic DN thymocytes
2010-01-22 | E-TABM-860 | biostudies-arrayexpress
Project description:Deregulated expression of oncogenic transcription factors is a common cause of T-cell acute lymphoblastic leukemia (T-ALL). However, the molecular and cellular effects of these transcription factors on developing T-cell progenitors are poorly understood. Here we show that the initial effect of the oncogenic transcription factor Lmo2 is to cause an almost complete block in differentiation at the DN2 stage of T-cell development.
2023-03-09 | GSE188225 | GEO
Project description:In this study, to investigate the pathogenic role of transcriptional regulator LMO2 during T lineage development, we isolated DN1, DN3, DP, CD4SP, CD8SP thymocytes, splenic CD4+ T cells and splenic CD8+ T cells from wild type and LMO2 over-expressing C57BL/6J mice for RNA-seq, and DN3 (CD25+), DP thymocytes, splenic CD4+/CD8+ T cells from transgenic mice and wild type DN3 (CD25+) thymocytes for ChIP-seq.
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Project description:To determine the requirement for Lyl1 in Lmo2-driven T-ALL, microarray data was perepared from sorted CD4-CD8 double negative thymocytes of wild-type, Lmo2 transgenic and Lmo2-transgenic, Lyl1 knockout mice. Total RNA obtained from sorted CD4-CD8 double-negative thymocytes
2013-07-25 | E-GEOD-49164 | biostudies-arrayexpress
Project description:To determine the requirement for Lyl1 in Lmo2-driven T-ALL, microarray data was perepared from sorted CD4-CD8 double negative thymocytes of wild-type, Lmo2 transgenic and Lmo2-transgenic, Lyl1 knockout mice.
2013-07-25 | GSE49164 | GEO
Project description:Prolonged or enhanced expression of the proto-oncogene Lmo2 is associated with a severe form of T-cell Acute Lymphoblastic Leukemia (T-ALL), designated Early T-progenitor ALL (ETP-ALL), that is characterized by the aberrant self-renewal and subsequent oncogenic transformation of immature thymocytes. Recent data suggest that Lmo2 may exert these effects by functioning as component of a multi-subunit transcription complex that includes the ubiquitous adapter Ldb1 along with b-HLH and/or GATA family transcription factors. In this study, we investigated the importance of Ldb1 for Lmo2-induced T-ALL by conditional deletion of Ldb1 in thymocytes in a Lmo2 transgenic mouse model of T-ALL. Our results identify a critical requirement for Ldb1 in the induction of thymocyte self-renewal, thymocyte radio-resistance and transition to T-ALL in Lmo2 transgenic mice. Ldb1 was also required for acquisition of the pre-leukemic ETP gene expression signature in immature Lmo2 transgenic thymocytes. Together, these results support a model where Lmo2-induced T-ALL results from failure to down-regulate Ldb/Lmo2 nucleated transcription complexes that normally function to enforce self-renewal in bone marrow hematopoietic progenitors
2020-03-19 | GSE129244 | GEO
Project description:Thymocytes from HEBAlt-transgenic mice expressing HA-tagged HEBAlt were subjected to IP using anti-HA, trypsin digested, and subjected to mass spectrometry
2022-05-27 | MSV000089563 | MassIVE
Project description:T-cell Acute Lymphoblastic Leukaemia (T-ALL) can be classified into a number of subfamilies, including those that overexpress TAL1/LMO, TLX1/3 and HOXA transcription factors. Whilst it has been previously shown in mouse models that TAL1/LMO transcription factors induce thymocyte self-renewal, whether this is the case for other transcription factor subclasses is currently unknown. To address this, we have studied vav-Nup98-HoxD13-transgenic (NHD13-Tg) mice, a model of HOXA-driven T-ALL, which overexpress HOXA transcription factors throughout haematopoiesis and display features of myelodysplastic syndrome in the bone marrow along with T-cell developmental abnormalities in the thymus and subsequent development of T-ALL in approximately 15% of mice. Thymocytes from preleukemic NHD13-Tg mice could engraft long-term in serial transplantation assays, demonstrating that NHD13-Tg thymocytes have acquired self-renewal capacity. Transcriptome analysis showed that NHD13-Tg thymocytes exhibited a Stem Cell like transcriptional program which closely resembled that of Lmo2 transgenic thymocytes, including Lmo2 itself and the critical Lmo2 cofactor Lyl1, suggesting a common mechanism of thymocyte self-renewal in these models. To determine whether Lmo2/Lyl1 are required for NHD13-induced thymocyte self-renewal, NHD13-Tg mice were crossed with Lyl1 knockout mice to generate NHD13-Tg mice lacking Lyl1. This showed that Lyl1 is essential for expression of the stem cell-like gene expression program in NHD13-Tg thymocytes and for thymocyte self-renewal. Surprisingly however, absence of Lyl1 accelerated the onset of T-ALL in NHD13-Tg mice. These studies demonstrate that Lyl1 is essential for self-renewal of NHD13-Tg thymocytes, suggesting that Lmo2 and Lyl1 may mediate thymocyte self-renewal induced by a variety of T-cell oncogenes. However, whilst Lyl1-induced thymocyte self-renewal is essential for Lmo2-driven T-cell leukemia, NHD13 can also promote T-ALL via an alternative pathway.
2019-03-04 | GSE121641 | GEO
Project description:Screening for mouse cDNA that was highly expressed in positive-selector H-2b AND-TCR-transgenic thymocytes using Affymetrix Murine Genome arrays. Keywords: transgenic mouse
2006-01-31 | GSE3909 | GEO
Project description:Lmo2 is an oncogenic transcription factor that is a frequent target of chromosomal abnormalities in this T-cell acute lymphoblastic leukemia (T-ALL). In transgenic mouse models, overexpression of Lmo2 causes thymocyte self-renewal leading to T-cell leukemia with long latency. However, the requirement of Lmo2 for maintenance of overt leukemia is poorly understood. We found that Lyl1, a critical cofactor for Lmo2-induced leukemia, is frequently lost in cell lines derived from Lmo2-transgenic mice, raising the possibility that Lmo2 function is dispensable at this stage. To study this, we developed a Tetracycline-repressible knock-in mouse model (Vav-TRE-Lmo2), which expresses Lmo2 throughout the haematopoietic system. This led to specific effects on T-cell development and the development of T-cell leukemia with long latency, preceded by the presence of self-renewing T-cells in the thymus. Repression of Lmo2 overcame the Lmo2-induced thymocyte developmental block at the preleukemic stage and led to elimination of Lmo2-induced thymocyte self-renewal in vivo. In contrast, Lmo2 function was dispensable for the majority of overt Lmo2-induced T-cell leukemias as well as leukemia-derived cell lines, implying an evolution of oncogene addiction in the majority of T-cell leukemias. Lmo2-dependence in T-ALL was associated with an immature gene expression profile, but could not be predicted by immunophenotype or assessment of Notch pathway activation. Thus, Lmo2 can give rise to both Lmo2-depenent and –independent T-cell leukemias. The Vav-TRE-Lmo2 model should be useful to determine the molecular features associated with Lmo2-dependence, as well as the critical components of the Lmo2-induced self-renewal pathways in T-ALL.
2022-01-01 | GSE125674 | GEO