Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE62144
PROVIDER: PRJNA263277 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The T-cell leukemia homeobox 1 (TLX1, HOX11) transcription factor is critically involved in the multistep pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and often cooperates with NOTCH1 activation during malignant T-cell transformation. However, the exact molecular mechanisms by which these T-cell specific oncogenes cooperate during transformation remain to be established. Here, we used an integrative genomics approach to show that the oncogenic properties of TLX1 are mediated by genome-wide interference with the ETS1 and RUNX1 transcription factors. Partial disruption of ETS1 and RUNX1 activity by ectopic TLX1 expression in immature thymocytes drives repression of T-cell specific super-enhancers and mediates an unexpected transcriptional antagonism with NOTCH1 signaling. These phenomena coordinately trigger a TLX1 driven pre-leukemic phenotype in human thymic precursor cells, which corresponds with the in vivo thymic regression observed in murine TLX1 tumor models, and creates a strong genetic pressure for acquiring activating NOTCH1 mutations as a prerequisite for full leukemic transformation. In conclusion, our results uncover a functional antagonism between cooperative oncogenes during the earliest phases of tumor development and provide novel insights in the multistep pathogenesis of TLX1 driven human leukemia. Gene expression was measured after TLX1 overexpression in human CD34+ T-cell progenitors cultured on an OP9-DLL1 feeder layer. Cells were collected after 72h of co-culture. This was performed for 2 independent thymus CD34+ donors.
2015-08-05 | E-GEOD-62143 | biostudies-arrayexpress
Project description:RNA-sequencing of CD34+ thymocytes that were cultured on an OP9-GFP or OP9-DLL1 feeder layer.
| PRJNA262922 | ENA
Project description:Gene expression analysis in Ebf1-/- lymphocyte progenitors complemented with EBF1wt or EBF1E271A and co-cultured with OP9-DL1 feeder cells.
2022-07-01 | GSE201528 | GEO
Project description:Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. CD34+ cells of 2 healthy donors are cultured on a OP9-GFP or OP9-DLL1 feeder layer.
2014-10-27 | E-GEOD-62000 | biostudies-arrayexpress
Project description:Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. CD34+ cells of 4 healthy donors are cultured on a OP9-GFP or OP9-DLL1 feeder layer.
2014-10-27 | E-GEOD-61871 | biostudies-arrayexpress
Project description:Umbilical cord blood (UCB) transplantation shows pro-angiogenic effect and contributes to symptom amelioration in animal models of cerebral infarction. OP9 is a stromal cell line used as feeder cells to promote hematoendothelial differentiation of embryonic stem cells. We co-cultured UCB 24hr with OP9 (i.e. OP9 preconditioning) and investigated its change in angiogenic properties and underlying mechanisms. Single cell RNA sequencing showed prominent phenotypic shift toward M2 in monocytic fraction of OP9 pre-conditioned UCB.
2023-01-25 | GSE207249 | GEO
Project description:Development of gene expression signatures with lncRNAs for coculture of CD34+ T-cells with an OP9-DLL1 feeder layer
| PRJNA262919 | ENA
Project description:Embryonic stem (ES) cells and ES cell-derived progeny characterized by nestin expression (including neural progenitors) were studied (three independent experiments). The mouse ES cell line R1 was cultured on a feeder layer of mouse embryonic fibroblasts (FL). ES cells were differentiated into nestin-positive cells for 4+8 days and 4+11 days according to the differentiation protocol by Rolletschek et al. (Mechanisms of Development 105, 93-104, 2001). The study was performed with three independent cell cultures (= triplicates). RNA was prepared from both undifferentiated ES cells and ES cell-derived nestin-positive cells, and from fibroblast feeder cells. Keywords = ES cell Keywords = nestin positive cells Keywords = feeder layer Keywords: other
2005-09-17 | GSE2375 | GEO
Project description:human corneal epithelial cells were isolated from healthy human donor eyes. Cells were cultured with irradiated 3T3 (i3T3) murine fibroblast feeder cells, irradiated human corneal fibroblasts (iHFL) or without feeder layer
2019-12-12 | GSE141841 | GEO
Project description:We used microarrays to perform a global gene expression analysis in Tcf1-expressing Thy1+CD25+ T lineage cells that develop on OP9 stroma in the absence of Notch1 signals. We compare this to the starting population, LMPP progenitors, and to control expressing T lineage cells that developed on OP9 stroma expressing Notch ligand DL4. The overall goal of this study was to determine if Tcf1 initiates T lineage specification in lymphoid progenitors. We found that Tcf1 was sufficient to upregulate many T lineage genes as compared to control expressing progenitors on OP9-DL4. Abstract of manuscript: The thymus imposes the T cell fate on incoming multipotent progenitors, but the molecular mechanisms are poorly understood. We show that transcription factor Tcf1 initiates T-lineage-specific gene expression. Tcf1 is downstream of Notch1 signaling and expressed in early T-cell progenitors. Progenitors deficient for Tcf1 are unable to initiate normal T-lineage specification. Conversely, ectopic expression of Tcf1 in hematopoietic progenitors is sufficient to induce expression of T-lineage specific genes in vitro. Thus, our study identifies Tcf1 as critically involved in the establishment T cell identity. Wiltype LMPPs were isolated by a FACSAria cell sorter and retrovirally transduced with a Tcf1-containing (Tcf1-VEX) or control vector (VEX) retrovirus. Tcf1-expressing cells and control-vector expressing cells were then seeded on OP9 stroma or OP9 stroma expressing Notch ligand DL4, respectively. On day 10, Thy1+CD25+ T lineage cells were sorted from Tcf1-expressing cells on OP9 stroma and compared to sorted LMPPs and Thy1+CD25+ T lineage cells that developed from control-vector expressing cells on OP9-DL4.
2011-08-03 | E-GEOD-26560 | biostudies-arrayexpress