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Mus musculus
4 Downloadable Samples
Illumina HiSeq 1000
Description
Hypoxia inducible factor-1a (HIF-1a) is a critical transcription factor for the hypoxic response, angiogenesis, normal hematopoietic stem cell regulation, and cancer development. Importantly, HIF-1a is also a key regulator for immune cell activation. In order to determine whether HIF-1a is sufficient for developing MDS phenotypes, we generated blood specific inducible HIF-1a transgenic mice. Using Vav1-Cre/Rosa26-loxP-Stop-loxP (LSL) rtTA driver, stable HIF-1a can be induced in a doxycycline administration dependent manner. After induction, HIF-1a-induced mice developed thrombocytopenia, leukocytopenia, macrocytic anemia, and multi-lineage dysplasia. We also found activation of both innate and adaptive immunity in HIF-1a- induced mice compared to those from control mice. Taken together, these data suggest that HIF-1a is sufficient to trigger a variety of key MDS features Overall design: Expression profiles of mRNA in HSPCs from constitutively active form of HIF1a protein induced mice and their control mice.
Publication Title
Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 1000
Description
The MLL-PTD mutation is found in patients with MDS and AML, and not in other hematological malignancies. Previously, we showed that Mll-PTD knock-in heterozygous mice (MllPTD/WT mice) present with several MDS-associated features. However, these phenotypes are insufficient to constitute bona fide MDS. MllPTD/WT mice do not generate MDS or AML in primary or transplant recipient mice. This suggests that additional genetic and/or epigenetic defects are necessary for transformation to MDS or AML. In secondary AML and de novo AML, MLL-PTD mutation is significantly associated with mutations in RUNX1 and with the FLT3-ITD mutations. In fact, the combination of MLL-PTD with the FLT3-ITD allele leads to AML in mice. We combined the MLL-PTD with RUNX1 mutant proteins, in order to generate a new mouse model for MDS. We generated MllPTD/WT/Runx1Flox/Flox/Mx1-Cre mice to model loss-of-function RUNX1 mutations. To test the significance of HIF-1a in this model, we also generated MllPTD/WT/Runx1Flox/Flox/Hif-1aFlox/Flox/Mx1-Cre mice and genetically eliminated Hif-1a expression. We analyzed gene expression variations in the HSPCs comparing the MllPTD/WT/Runx1?/? with or without HIF-1a abrogation. Overall design: Expression profiles of mRNA in HSPCs from MLL-PTD/Runx1-KO mice with or without HIF-1a
Publication Title
Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 12 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Gene expression profiling in dopaminergic brain structures of rats self-administering cocaine. Effect of histone deacetylase inhibition
Publication Title
Inhibition of histone deacetylases in rats self-administering cocaine regulates lissencephaly gene-1 and reelin gene expression, as revealed by microarray technique.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
The nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes. Overall design: RNA profiles in wild-type and Taf4-/- livers by deep sequencing
Publication Title
TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina humanRef-8 v1.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional re-programming of primary macrophages reveals distinct apoptotic and anti-tumoral functions of IRF-3 and IRF-7.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina humanRef-8 v1.0 expression beadchip
Description
Determine the role of interferons in the transcriptional profile of Ad-F7 transduced primary human macrophages using neutralizing antibody for the type I IFN receptor (IFNAR2).
Publication Title
Transcriptional re-programming of primary macrophages reveals distinct apoptotic and anti-tumoral functions of IRF-3 and IRF-7.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Increased expression of Kruppel like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. The contribution of KLF7 to hematopoiesis has not been previously described. Herein, we characterized the effect on murine hematopoiesis of the loss of KLF7 and enforced expression of KLF7. Long-term multilineage engraftment of Klf7-/- cells was comparable to control cells, and self-renewal, as assessed by serial transplantation, was not affected. Enforced expression of KLF7 results in a marked suppression of myeloid progenitor cell growth and a loss of short- and long-term repopulating activity. Interestingly, enforced expression of KLF7, while resulting in multi-lineage growth suppression that extended to hematopoietic stem cells and common lymphoid progenitors, spared T cells and enhanced the survival of early thymocytes. RNA expression profiling of KLF7-overexpressing hematopoietic progenitors identified several potential target genes mediating these effects. Notably, the known KLF7 target Cdkn1a (p21Cip1/Waf1) was not induced by KLF7, and loss of CDKN1A does not rescue the repopulating defect. These results suggest that KLF7 is not required for normal hematopoietic stem and progenitor (HSPC) function, but increased expression, as seen in a subset of lymphoid leukemia, inhibits myeloid cell proliferation and promotes early thymocyte survival.
Publication Title
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Increased expression of Kruppel like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. The contribution of KLF7 to hematopoiesis has not been previously described. Herein, we characterized the effect on murine hematopoiesis of the loss of KLF7 and enforced expression of KLF7. Long-term multilineage engraftment of Klf7-/- cells was comparable to control cells, and self-renewal, as assessed by serial transplantation, was not affected. Enforced expression of KLF7 results in a marked suppression of myeloid progenitor cell growth and a loss of short- and long-term repopulating activity. Interestingly, enforced expression of KLF7, while resulting in multi-lineage growth suppression that extended to hematopoietic stem cells and common lymphoid progenitors, spared T cells and enhanced the survival of early thymocytes. RNA expression profiling of KLF7-overexpressing hematopoietic progenitors identified several potential target genes mediating these effects. Notably, the known KLF7 target Cdkn1a (p21Cip1/Waf1) was not induced by KLF7, and loss of CDKN1A does not rescue the repopulating defect. These results suggest that KLF7 is not required for normal hematopoietic stem and progenitor (HSPC) function, but increased expression, as seen in a subset of lymphoid leukemia, inhibits myeloid cell proliferation and promotes early thymocyte survival.
Publication Title
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.
Sample Metadata Fields
Specimen part
View Samples
GSE40324- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Increased expression of Kruppel like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. The contribution of KLF7 to hematopoiesis has not been previously described. Herein, we characterized the effect on murine hematopoiesis of the loss of KLF7 and enforced expression of KLF7. Long-term multilineage engraftment of Klf7-/- cells was comparable to control cells, and self-renewal, as assessed by serial transplantation, was not affected. Enforced expression of KLF7 results in a marked suppression of myeloid progenitor cell growth and a loss of short- and long-term repopulating activity. Interestingly, enforced expression of KLF7, while resulting in multi-lineage growth suppression that extended to hematopoietic stem cells and common lymphoid progenitors, spared T cells and enhanced the survival of early thymocytes. RNA expression profiling of KLF7-overexpressing hematopoietic progenitors identified several potential target genes mediating these effects. Notably, the known KLF7 target Cdkn1a (p21Cip1/Waf1) was not induced by KLF7, and loss of CDKN1A does not rescue the repopulating defect. These results suggest that KLF7 is not required for normal hematopoietic stem and progenitor (HSPC) function, but increased expression, as seen in a subset of lymphoid leukemia, inhibits myeloid cell proliferation and promotes early thymocyte survival.
Publication Title
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function.
Sample Metadata Fields
Specimen part
View Samples