Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA262919 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:RNA-sequencing of CD34+ thymocytes that were cultured on an OP9-GFP or OP9-DLL1 feeder layer.
| PRJNA262922 | ENA
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:Development of gene expression signatures for TLX1 overexpression in human thymus C34+ T-cell progenitors cultured on an OP9-DLL1 feeder layer
| PRJNA263277 | ENA
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:The OP9 coculture system is widely used to differentiate pluripotent stem cells into mesodermal lineages. We used single cell RNA sequencing to analyze differentiation trajectories and heterogeniety of differentiating pluripotent stem cells using the OP9 coculture system.
2024-07-10 | GSE271441 | GEO
Project description:PHF6 keeps hematopoietic lineage development in check [OP9-DLL1]
| PRJNA338297 | ENA
Project description:CD34+ cord blood hematopoietic progenitors were expanded in vitro as previously described (Balan et al., J Immunol, 2014) and then differentiated on a mixed feeder layer of OP9 cells expressing or not the Notch ligand Delta-like 1, with FLT3-L, TPO and IL-7. At the end of the cultures, single live Lin- HLA-DR+ cells were index sorted in 96-well plates containing lysis buffer, and snap frozen. Four putative cell types were sorted according to their expression patterns of key combinations of cell surface markers: putative pDCs, putative cDC1s, putative pre-cDC2s and putative cDC2s. Single cell RNA-sequencing libraries were subsequently generated for 90 single cells and 6 control wells using an adaptation of Smart-Seq2 (Villani et al., Science, 2017). Cells were sequenced at a depth of 1-3M reads/cell.
2018-08-14 | GSE108546 | GEO
Project description:We have developed efficient protocols for the derivation of mesenchymal precursors from hESCs. While previous protocols were based on mesodermal induction via co-culture of hESCs on OP9 mouse stroma (Barberi et al., PLoS Biology, 2005), our recent work shows the derivation of hESC derived mesenchymal precurors under feeder-free conditions. The data presented here show a large and highly signficant overlap in global gene expression profiles between hESC derived mesenchymal precursors derived under feeder-free conditions with those derived via OP9 co-culure and mesenchymal precurosrs isolated directly from the adult bone marrow. Experiment Overall Design: These data compare the gene expression profiles of hESC derived mesenchymal precursors derived via the OP9 protocol, with those obtained under feeder-free conditions and adult bone marrow derived mesenchymal precursors. Three samples of undifferentiated hESCs are used for subtracting genes to define mesenchymal precurosr cell specific signatures (see Barberi et al. Nature Medicine 2007 for details).
2008-06-15 | E-GEOD-7332 | biostudies-arrayexpress
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