Medial HOXA gene expression is a landmark for the definitive haematopoietic fate and a prerequisite for human HSC function
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Hanna Mikkola
PROVIDER: E-GEOD-76685 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:The derivation of functional, transplantable HSCs from an pluripotent stem cells in vitro holds great promise for clinical therapies, but is unachieved. In order to achieve full functionality of HSCs, it is vital to determine the extent to which PSCs can currently be differentiated to the HSC program in vitro and identify the remaining dysregulated genetic pathways. Microarrays were used to compare the transcritomes of ESC-derived immunophenotypic HSPCs to endogenous HSPCs from various stages of development to determine the programs important for human HSC development and function, and which programs were lacking in ESC-derived hematopoietic cells. CD34+CD38-CD43+CD90+ HSPCs were sorted from human placenta and embryoid bodies, and CD34+CD38-CD45+CD90+ HSPCs sorted from fetal liver and embryoid bodies co-cultured on OP9-M2 stroma, the RNA was extracted, library created and hybridized to the Affymetrix microarray
2016-05-16 | E-GEOD-64865 | biostudies-arrayexpress
Project description:RA signalling regulated endothelial to hematopoietic transition and HSC generation. EB- or FL-derived HSPC were profiled before (d0) or after (d6) 6 days of treatment with 0.2uM AM580 on OP9, and after 6 additional days of expandion of OP9 (d12) without treatment.
2016-05-16 | E-GEOD-76682 | biostudies-arrayexpress
Project description:HOXA7 regulates FL-HSPC self-renewal in vitro and in vivo. We profiled EB-HSPCs after HOXA7 overexpression (EB-HOXA7), or with a control vector (EB-CTR), to assess the gene expression programs regulated by HOXA7. CD34+CD38-CD43+CD90+ HSPCs were infected with lentiviral FUGW vector either empty (FUGW-GFP) or encoding HOXA7(FUGW-GFP-HOXA7) protein. Cells were expanded on op9 for 15 days and than sorted for GFP HSPC immunophenotype.
2016-05-16 | E-GEOD-76684 | biostudies-arrayexpress
Project description:One of the long-standing goals in the field has been to establish a culture system that would allow maintenance of HSC properties ex vivo. In the absence of such system, the ability to model human hematopoiesis in vitro has been limited, and there has been little progress in the expansion of human HSCs for clinical application. To that end, we defined a mesenchyml stem cell co-culture system for expansion of clonally multipotent human HSPCs that are protected from apoptosis and immediate differentiation, and retain the HSPC phenotype. By performing a genome-wide gene expression analysis of purified HSPCs isolated at different stages of co-culture, we asked at the molecular level, to what degree hematopetic stem cell properties can be preserved during culture. This temporal gene expression data from in vivo derived- and ex vivo expanded human HSPCs will serve as a resource to identify novel regulatory pathways that control HSC properties, and to develop clinically applicable protocols for HSC expansion. Human CD34+ fetal liver cells were co-cultured on a subclone of OP9 stomal cells (OP9M2 sublemented with supportive cytokines (see below)). To distinguish between molecular changes acquired over prolonged culture versus immediately after exposure to culture, gene expression in isolated CD45+CD34+CD38-CD90+ HSPCs was assessed after 12 hours, 2 weeks and 5 weeks in culture. Cultured CD45+CD34+CD38-CD90+HSPCs were compared to freshly isolated CD45+CD34+CD38-CD90+HSPCs and their more differentiated CD45+CD34+CD38+CD90- downstream progenitor cells.
2013-01-31 | E-GEOD-34972 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-01-31 | E-GEOD-34974 | 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 2 healthy donors are cultured on a OP9-GFP or OP9-DLL1 feeder layer.
2014-10-27 | E-GEOD-62000 | biostudies-arrayexpress
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: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:Purpose: To characterize transcriptional changes associated with inhibition of Dot1l in 2 inv(16) patient AML samples Methods: We sequenced mRNA from patient samples that were exposed to 5 uM EPZ004777 or DMSO control for 7 days. Results: Inhibition of Dot1l leads to gene expression changes in genes related to cell growth and cell cycle. Examination of mRNA levels between cells treated with 5 uM EPZ004777 or DMSO control
2016-01-12 | E-GEOD-76747 | biostudies-arrayexpress
Project description:Comparison of panel of miRNA from megakaryocitic cell line at two different stage : Adult and Embryonnic
2013-12-31 | E-MEXP-3816 | biostudies-arrayexpress