This SuperSeries is composed of the SubSeries listed below.
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Specimen part, Cell line
View SamplesWe performed whole genome expression analysis using BCR/ABL expressing Kit+ cells derived from wild type and ROSACreERT2c-Fosfl/flDusp1-/- bone marrow cells. Wild type kit+ cells were treated with DFC+BCI and DFC+BC+Im to mimic the genetic loss of c-Fos and Dusp1. Overall design: The experiment was designed to test whether chemical inhibition by FOS and Dusp1 Inhibitor mimics the genetic deletion of cFOS and Dusp1 in mouse primary cells transduced with BCR-ABL. This data is part of the super series Mechanism of Oncogene addiction GSE75058.
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Specimen part, Cell line, Subject
View SamplesThe Baf3 are dependent on IL-3 for grwoth however transformation by BCR -ABL oncogene causes BAf3 cells independent of IL-3. The BAf3 cells expressing BCR-ABL are dependent on continuous expression of BCR_ABL for growth. Inhibitionof BCR-ABL by its inhibitor Imatinib cause these cells to undergo apoptosis. When these cells are grown with IL-3 these cells do not respond to Imatinib mediated grwoth arrest.
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Cell line
View SamplesK562 cells when grown with erythropeitin do not respond to Imatinib. Here we are comparing the gene expression profile from imatinib resistant and sensitive cells.
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Cell line
View SamplesBAF3 cells harboring constitutively expressing BCR-ABL were grown with or without IL-3 supplement and treated with Imatinib and live cells from the IL-3 and without IL-3 were sorted by FACS.
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Alternative generation of CNS neural stem cells and PNS derivatives from neural crest-derived peripheral stem cells.
Specimen part
View SamplesNeural crest-derived neural stem cells (NCSCs) from the embryonic PNS can be reprogrammed in neurosphere culture (NS) to rNCSCs that produce CNS progeny, including myelinating oligodendrocytes. Using global gene expression analysis we now demonstrate that rNCSCs completely lose their previous PNS characteristics and acquire the identity of neural stem cells derived from embryonic spinal cord (SCSCs). Reprogramming proceeds rapidly and results in a homogenous population of Olig2-, Sox3- and Lex-positive CNS stem cells. Low-level expression of pluripotency inducing genes Oct4, Nanog and Klf4 argues against a transient pluripotent state during reprogramming. The acquisition of CNS properties is prevented in the presence of BMP4 (BMP NCSCs) as shown by marker gene expression and the potential to produce PNS neurons and glia. In addition, genes characteristic for mesenchymal and perivascular progenitors are expressed, which suggests that BMP NCSCs are directed towards a pericyte progenitor/mesenchymal stem cell (MSC) fate. Adult NCSCs from mouse palate, an easily accessible source of adult NCSCs, display strikingly similar properties. They do not generate cells with CNS characteristics but lose the neural crest markers Sox10 and p75 and produce MSCs. These findings show that embryonic NCSCs acquire a full CNS identity in neurosphere culture. In contrast, MSCs are generated from adult pNCSCs and BMP NCSCs, which reveals that postmigratory NCSCs are a source for MSCs up to the adult stage.
Alternative generation of CNS neural stem cells and PNS derivatives from neural crest-derived peripheral stem cells.
Specimen part
View SamplesNeural crest-derived neural stem cells (NCSCs) from the embryonic PNS can be reprogrammed in neurosphere culture (NS) to rNCSCs that produce CNS progeny, including myelinating oligodendrocytes. Using global gene expression analysis we now demonstrate that rNCSCs completely lose their previous PNS characteristics and acquire the identity of neural stem cells derived from embryonic spinal cord (SCSCs). Reprogramming proceeds rapidly and results in a homogenous population of Olig2-, Sox3- and Lex-positive CNS stem cells. Low-level expression of pluripotency inducing genes Oct4, Nanog and Klf4 argues against a transient pluripotent state during reprogramming. The acquisition of CNS properties is prevented in the presence of BMP4 (BMP NCSCs) as shown by marker gene expression and the potential to produce PNS neurons and glia. In addition, genes characteristic for mesenchymal and perivascular progenitors are expressed, which suggests that BMP NCSCs are directed towards a pericyte progenitor/mesenchymal stem cell (MSC) fate. Adult NCSCs from mouse palate, an easily accessible source of adult NCSCs, display strikingly similar properties. They do not generate cells with CNS characteristics but lose the neural crest markers Sox10 and p75 and produce MSCs. These findings show that embryonic NCSCs acquire a full CNS identity in neurosphere culture. In contrast, MSCs are generated from adult pNCSCs and BMP NCSCs, which reveals that postmigratory NCSCs are a source for MSCs up to the adult stage.
Alternative generation of CNS neural stem cells and PNS derivatives from neural crest-derived peripheral stem cells.
Specimen part
View SamplesPurpose: Analyze the function of the transcription factors Hand2 and Gata3 in adult sympathetic neurons by induced knockout and RNAseq analysis Overall design: Method and Result: Hand2flx/del::DbhCreERT2 (referred to as mutant) and Hand2flx/+::DbhCreERT2 (referred to a control) were injected for 10 days with tamoxifen to activate Cre. Animals were killed, sympathetic ganglia (SCG+Stellate) collected and processed for RNA isolation and RNAseq (Stanzel et al., 2016). Gata3flx/flx::DbhCerERT2 (mutant) and Gata3flx/+::DbhCreERT2 (controls) were treated as Hand2 animals. 16 ganglia from 4 mice were pooled for Hand2 mutant and controls and Gata3 controls. As only rudimentary ganglia were present in Gata3 mutant mice (Tsarovina et al., 2010) ganglia from 8 mice were pooled. The specific effects of the Hand2 knockout are decribed in Stanzel et al., 2016. The analysis of ganglion rudiments in the Gata3 knockout revealed that Gata3 was not reduced, indicating that the remaining cells had escaped the knockout.
Distinct roles of hand2 in developing and adult autonomic neurons.
Specimen part, Subject
View SamplesLung cancer is a leading cause of deaths in the world. There is a need to improve an understanding of mechanisms of malignant transformation and to develop genetic markers of disease for better and targeted therapies.
Cancer genomics identifies regulatory gene networks associated with the transition from dysplasia to advanced lung adenocarcinomas induced by c-Raf-1.
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