Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA165135 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The first genetic hits towards leukemia are thought often to confer to the mutant clone a slight proliferative/survial advantage. These pre-malignant clones can then be maintained under physiological cues in normal pool for long periods. We have searched for this type of first genetic hits and found that ectopic expression of novel nucleoporin 98 (NUP98)-homeodomain fusion proteins in primitive bone marrow cells can induce long-lasting hematopoietic stem cell (HSC) activity in these cells. More specifically, NUP98-CDX1/2 was able to sustain HSC activity with high frequencies despite massive in vitro expansions and in vivo residence. Continual expression of NUP98-CDX1/2 did not perturb lymphoid, myeloid or erythroid/platelet differentiation and NUP98-CDX1/2 was able to reprogram committed progenitors into cells with attributes of HSC. Switching off of NUP98-CDX1/2 expression did not lead to “return” to normal HSC but acute differentiation. Related NUP98-CDX4 induced leukemia with the shortest latency ever reported for HOX transcription factors. In this case switching off of NUP98-CDX4 expression cured the full-blown leukemia and again the cured cells showed only transient repopulating activity in vivo. These two types of pre-leukemic cells generated here will provide useful models for elucidating the self-renewal mechanisms of HSC as well as leukemic stem cells. Total RNA from NUP98-CDX lines was compared to EGFP overexpressing lines. The experiment was done in triplicate.
2012-12-01 | E-GEOD-37900 | biostudies-arrayexpress
Project description:The first genetic hits towards leukemia are thought often to confer to the mutant clone a slight proliferative/survial advantage. These pre-malignant clones can then be maintained under physiological cues in normal pool for long periods. We have searched for this type of first genetic hits and found that ectopic expression of novel nucleoporin 98 (NUP98)-homeodomain fusion proteins in primitive bone marrow cells can induce long-lasting hematopoietic stem cell (HSC) activity in these cells. More specifically, NUP98-CDX1/2 was able to sustain HSC activity with high frequencies despite massive in vitro expansions and in vivo residence. Continual expression of NUP98-CDX1/2 did not perturb lymphoid, myeloid or erythroid/platelet differentiation and NUP98-CDX1/2 was able to reprogram committed progenitors into cells with attributes of HSC. Switching off of NUP98-CDX1/2 expression did not lead to “return” to normal HSC but acute differentiation. Related NUP98-CDX4 induced leukemia with the shortest latency ever reported for HOX transcription factors. In this case switching off of NUP98-CDX4 expression cured the full-blown leukemia and again the cured cells showed only transient repopulating activity in vivo. These two types of pre-leukemic cells generated here will provide useful models for elucidating the self-renewal mechanisms of HSC as well as leukemic stem cells.
2012-12-01 | GSE37900 | GEO
Project description:We have cloned and characterized a fusion gene NUP98/HHEX1 resulting from t(7;10) from a patient with acute myeloid leukemia (AML). As NUP98/HHEX acts as an aberrant transcriptional activator, putative targets were searched upon transient expression of the fusion in primary murine bone marrow cells. Keywords: Comparative analysis of NUP98/HHEX, NUP98/HOX vs. MIG (empty virus) in primary bone marrow cells
2008-04-01 | GSE10909 | GEO
Project description:We have cloned and characterized a fusion gene NUP98/HHEX1 resulting from t(7;10) from a patient with acute myeloid leukemia (AML). As NUP98/HHEX acts as an aberrant transcriptional activator, putative targets were searched upon transient expression of the fusion in primary murine bone marrow cells. Experiment Overall Design: Murine bone marrow cells were transduced with a retrovirus (MSCV-IRES-GFP, MIG) expressing either NUP98/HHEX or NUP98/HOXA9 (or the empty vector), mRNA was isolated after 72h. Each experiment was performed in triplicates.
2008-06-11 | E-GEOD-10909 | biostudies-arrayexpress
Project description:To provide the first insight into the pathophysiological relevance of the Nizp1-NSD1 functional association, we targeted this interaction in the context of acute myeloid leukemia driven by the expression of NUP98-NSD1 oncogenic fusion. We expressed NUP98-NSD1 in mouse c-Kit+/Sca-1+/Lin- bone marrow progenitors and knocked down Nizp1 expression by shRNA. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different cell lines.
2023-02-07 | GSE209850 | GEO
Project description:Leukemia is a complex malignancy with hundreds of distinct mutations associated with disease development. Studies have shown that oncogenes cooperate to promote leukemia transformation, however, the downstream effectors of this cooperation are largely unknown. Using a genetically defined mouse model of acute leuekmia, we investigated the regulated of genes downstream of the cooperative oncogenic interaction between BCR-ABL and NUP98-HOXA9 and identified a unique gene signature abberrantly expression in leukemia. Total RNA was isolated from hematopoietic cells transduced with BCR-ABL and Nup98-HOXA9 retroviruses and transplanted into recipient mice. Bone marrow cells were purified by GFP (BCR-ABL) and YFP (NUP98-HOXA9) using FACS.
2012-05-10 | E-GEOD-37907 | biostudies-arrayexpress
Project description:Trascriptional profiling by array of bone marrow derived murine cells trasduced with control and Id1-overexpressing vectors to identify genes changes induced by increased expression of the transcriptional regulator Id1
2015-03-31 | E-MTAB-2280 | biostudies-arrayexpress
Project description:original population (oMSC) and highly migrative subpopulation (sMSC) of murine eGFP+ bone marrow MSC
| EGAD00010001265 | EGA
Project description:BACKGROUND: Hox genes are implicated in hematopoietic stem cell (HSC) regulation as well as in leukemia development through translocation with the nucleoporin gene NUP98. Interestingly, an engineered NUP98-HOXA10 (NA10) fusion can induce a several hundred-fold expansion of HSCs in vitro and NA10 and the AML-associated fusion gene NUP98-HOXD13 (ND13) have a virtually indistinguishable ability to transform myeloid progenitor cells in vitro and to induce leukemia in collaboration with MEIS1 in vivo. METHODOLOGY/PRINCIPAL FINDINGS: These findings provided a potentially powerful approach to identify key pathways mediating Hox-induced expansion and transformation of HSCs by identifying gene expression changes commonly induced by ND13 and NA10 but not by a NUP98-Hox fusion with a non-DNA binding homedomain mutation (N51S). The gene expression repertoire of purified murine bone marrow Sca-1+Lin- cells transduced with retroviral vectors encoding for these genes was established using the Affymetrix GeneChip MOE430A. Approximately seventy genes were differentially expressed in ND13 and NA10 cells that were significantly changed by both compared to the ND13(N51S) mutant. Intriguingly, several of these potential Hox target genes have been implicated in HSC expansion and self-renewal, including the tyrosine kinase receptor Flt3, the prion protein, Prnp, hepatic leukemia factor, Hlf and Jagged-2, Jag2. CONCLUSIONS: In conclusion this study has identified several novel Hox downstream target genes and provides important new leads to key regulators of the expansion and transformation of hematopoietic stem cells by Hox. Experiment Overall Design: Adult murine bone marrow cells transduced with vectors carrying ND13, NA10, ND13(N51S) or an empty GFP control vector (MIG) were isolated on the basis of GFP expression by FACS 24 hours post-transduction. Viable transduced cells were further enriched for primitive hematopoietic cells by exclusion of cells expressing linage markers (Gr-1, B220, Ter-119, CD4, CD5 and CD8) and selection for cells expressing the stem cell antigen-1 (Sca-1). Three independent experiments were performed for each of the four different conditions included in the study.
2008-06-17 | E-GEOD-9079 | biostudies-arrayexpress
Project description:Using a stromal cell free system, we described the gene expression and two genome wide epigenetic profiles of a unique population of undifferentiated bone marrow cells selectively driven towards the T cell differentiation pathway Undifferentiated bone marrow cells, transduced with NUP98-HOXB4 fusion protein, in vitro expanded with IL6 and SCF represents the hematopoietic stem cells (HSC); when grown in the presence of DLL4 (Notch1 ligand) and IL7, they are directed towards the T cell lineage (ProT); these in vitro generated ProT cells injected in a Rag2-/- mouse give rise to mature double positive T cells (DP). 2 replica for each population
2013-12-25 | E-GEOD-47995 | biostudies-arrayexpress