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Mus musculus
11 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
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.
Publication Title
Candidate genes for expansion and transformation of hematopoietic stem cells by NUP98-HOX fusion genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Total bone marrow (BM) from miR-223 knockout (mir-223-/-) and wildtype (miR-223+/+) mice 21 was extracted, prestimulated for 2 days. Then, the BM cells were simultaneously cotransduced with MSCV-Hoxa9-pgk-neomycin and a MSCV-Meis1-IRES-YFP by co-cultivation with irradiated (4,000 cGy) viral producers. HoxA9-Meis1 transduced cells were sorted for YFP expression and continuously selected with neomycin (1.4 mg/ml).
Publication Title
Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The molecular mechanism defining susceptibility of normal cells to oncogenic transformation may be a valuable therapeutic target. We characterized the cell of origin and its critical pathways in MN1 leukemias. Common myeloid (CMP), but not granulocyte-macrophage progenitors (CMP) could be transformed by constitutively overexpressed MN1. Complementation studies of CMP-signature genes in GMPs demonstrated that leukemogenicity of MN1 required the MEIS1/abdB-like HOX protein complex. Colocalization studies by ChIP-seq identified common chromatin targets of MN1 and MEIS1 that were associated with open chromatin and transcriptional activation. Transcriptional repression of MEIS1 target sites in established MN1 leukemias had antileukemic activity. As MN1 relies on but can not activate expression of MEIS1/abdB-like HOX proteins, transcriptional activity of these genes determines which cell is the cell of origin in MN1 leukemia.
Publication Title
Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Expansion of multipotent stem cells from the adult human brain.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples
GSE41467- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
Tissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells.
Publication Title
Expansion of multipotent stem cells from the adult human brain.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples GSE41468- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
Tissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells.
Publication Title
Expansion of multipotent stem cells from the adult human brain.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples GSE41394- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Tissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells.
Publication Title
Expansion of multipotent stem cells from the adult human brain.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples GSE41390- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Tissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells.
Publication Title
Expansion of multipotent stem cells from the adult human brain.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
The simultaneous genotyping of tens of thousands of SNP using SNP microarrays is a very important tool that is revolutionizing genetics and molecular biology. In this work, we present a new application of this technique by using it to assess chromatin immunoprecipitation (CHIP) as a means to assess the multiple genomic locations bound by a protein complex recognized by an antibody. We illustrate the use of this technique with an analysis of the change in histone H4 acetylation, a marker of open chromatin and transcriptionally active genomic regions, which occur during the differentiation of human myoblasts into myotubes. Our results are validated by the observation of a significant correlation between the histone modifications detected and the expression of the nearby genes, as measured by DNA microarrays.
Publication Title
ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression was determined for both myotubes and myoblasts using Affymetrix HG-U133 A/B arrays.
Publication Title
ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation.
Sample Metadata Fields
No sample metadata fields
View Samples