Background: Isolation and characterization of tumourigenic colon cancer initiating cells may help to develop novel diagnostic and therapeutic procedures. Methods: We characterized a panel of fourteen human colon carcinoma cell lines and their corresponding xenografts for the surface expression of different potential stem cell markers: CD133, CD24, CD44, CDCP1 and CXCR4. In five cell lines and nine xenografts mRNA expression of the investigated markers was determined. Tumour growth behaviour of CD133+, CD133- and unsorted SW620 cells was evaluated in vivo. Results: All surface markers showed distinct expression patterns in the examined tumours. Analyses of the corresponding xenografts revealed a significant reduction of cell numbers expressing the investigated markers. CD44 and CXCR4 mRNA expression correlated within the cell line panel and CD44 and CDCP1 within the xenograft panel, respectively. Small subpopulations of double and triple positive cells could be described. SW620 showed significantly higher take rates and shorter doubling times in vivo when sorted for CD133 positivity. Conclusion: Our data support the hypothesis of a small subset of cells with stem cell-like properties characterized by a distinct surface marker profile. In vivo growth kinetics give strong relevance for an important role of CD133 within the mentioned surface marker profile.
Characterization of colon cancer cells: a functional approach characterizing CD133 as a potential stem cell marker.
Sex, Age, Specimen part
View SamplesWe performed microarray analysis in order to evaluate the combination effect of the mitochondrial matrix chaperone inhibitor gamitrinib-triphenylphosphonium (G-TPP) and Liver X receptor agonist LXR623 on gene expression in stem cell like glioma cells (NCH644).
Activation of LXR Receptors and Inhibition of TRAP1 Causes Synthetic Lethality in Solid Tumors.
Specimen part, Cell line, Treatment
View SamplesQuiescent stem cells are periodically activated to maintain tissue homeostasis or occasionally called into action upon injury. Molecular mechanisms that constitutively maintain stem cell identity or promote stem cell proliferation and differentiation upon activation have been extensively studied. However, it is unclear how quiescent stem cells maintain identity and reinforce quiescence when they transition from quiescence to activation. Here we show mouse hair follicle stem cell compartment induces a transcription factor, Foxc1, when activated. Importantly, deletion of Foxc1 in the activated but not quiescent stem cells compromises stem cell identity, fails to re-establish quiescence and subsequently drives premature stem cell activation.These findings uncover a dynamic, cell-intrinsic mechanism employed by hair follicle stem cells to reinforce stemness in response to activation. Overall design: Poly(A)-enriched transcriptome RNA-seq on HFSCs isolated in WT and K14Cre cKO mice at anagen and early telogen stage of hair cycle.
Foxc1 reinforces quiescence in self-renewing hair follicle stem cells.
No sample metadata fields
View SamplesU87 cells were transduced with IDH1 WT or IDH1 R132H and stable clones were selected.
Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional code and disease map for adult retinal cell types.
Specimen part
View SamplesBrain circuits are assembled from a large variety of morphologically and functionally diverse cell types. It is not known how the intermingled cell types of individual brain regions differ in their expressed genomes. Here we describe an atlas of cell type transcriptomes of the adult retina. We found that each adult cell type expresses a specific set of genes, including a unique set of transcription factors, forming a barcode for cell identity. Cell type transcriptomes carry enough information to categorize cells into corresponding morphological classes and types. Surprisingly, several barcode genes are eye disease-associated genes that we demonstrate to be specifically expressed not only in photoreceptors but also in particular retinal circuit elements such as inhibitory neurons as well as in retinal microglia. Our data suggest that distinct cell types of individual brain regions are characterized by marked differences in their expressed genomes.
Transcriptional code and disease map for adult retinal cell types.
Specimen part
View SamplesBrain circuits are assembled from a large variety of morphologically and functionally diverse cell types. It is not known how the intermingled cell types of individual brain regions differ in their expressed genomes. Here we describe an atlas of cell type transcriptomes of the adult retina. We found that each adult cell type expresses a specific set of genes, including a unique set of transcription factors, forming a barcode for cell identity. Cell type transcriptomes carry enough information to categorize cells into corresponding morphological classes and types. Surprisingly, several barcode genes are eye disease-associated genes that we demonstrate to be specifically expressed not only in photoreceptors but also in particular retinal circuit elements such as inhibitory neurons as well as in retinal microglia. Our data suggest that distinct cell types of individual brain regions are characterized by marked differences in their expressed genomes.
Transcriptional code and disease map for adult retinal cell types.
Specimen part
View SamplesTo assess the effect of different forms of TL1A within different organs of the mouse we generated 2 different transgenic mouse lines where TL1A was expressed under the control of the CD2 promoter. 2 forms of TL1A was used. Either WT TL1A, which led to over expression of both membrane bound and soluble forms of TL1A (Refered to as Mem+Sol) or TL1A Delta 69-93 which only overexpressed membrane restricted TL1A (Refered to as Mem). Lungs and terminal ileums were taken from Either Mem, Mem+sol or WT litermate control mice at 12 weeks of age and the transcriptome assessed using RNAseq Through this we demonstrated enrichment of different transcripts and pathways both dependent on and independent of the form of TL1A and the site of action. This study is also the first to use RNASeq to assess the resualt of overexpression of TL1A within the mouse. Overall design: Poly-A purified mRNA profiles from the Ileum and Lung of Mem, Mem+Sol and WT mice generated using Illumina based RNASeq
Cleavage of TL1A Differentially Regulates Its Effects on Innate and Adaptive Immune Cells.
Sex, Specimen part, Subject
View SamplesTranscriptional profiling of guard cells and mesophyll cells in response to ABA treatment
Isolation of a strong Arabidopsis guard cell promoter and its potential as a research tool.
Specimen part, Disease, Disease stage, Compound
View SamplesSomatic mutations activating MAPK signaling in disorders of brain overgrowth and in diffuse glioma have recently been reported in pediatric neurology. Here we developed a progressive zebrafish model of glioma based on somatic expression of oncogenes that activate MAPK-AKT signalling (H-RASG12V, K-RASG12D, AKT, EGFRv3, BRAFV600E) in neural progenitor cells. Oncogenic HRAS was the most effective in activating MAPK signaling and caused the development of different types of growth disorders in juvenile fish: from benign dysplasia/heterotopia to invasive tumors of the telencephalon, midbrain and cerebellum. We used this model to clarify the molecular events leading to malignant tumors instead of benign lesions. Specific signatures distinguish benign heterotopia from tumors and establish that tumors require persistent activation of MAPK/ERK. Moreover, analysis of global RNA expression showed that brain tumors expressed a gene signature similar to the mesenchymal glioblastoma subtype Overall design: We performed transcriptome analysis (RNA-Seq) of 3 UAS:HRASV12G brains, which carried tumorigenic lesions in the telencephalon, midbrain and IV ventricle and compared them with tumor free, age matched brains.
A novel brain tumour model in zebrafish reveals the role of YAP activation in MAPK- and PI3K-induced malignant growth.
No sample metadata fields
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