A large body of evidence has demonstrated that many human tumors are maintained by a small cell population called cancer stem cells (CSCs) or tumor progenitors, which are responsible for tumor formation, therapy resistance and metastasis. We found that ionizing radiation treatment enriches for the CSC phenotype and properties by preferential survival and expansion of tumor progenitor cells. Our studies revealed that aldehyde dehydrogenase (ALDH) activity is indicative of prostate tumor progenitor cells with increased chemo- and radioresistance, enhanced migratory potential, improved DNA- double strand break repair and activation of the signaling pathways, which promote self-renewal and epithelial-mesenchymal transition. We found that X-ray irradiation can convert the bulk tumor cells to more clonogenic and radioresistant population positive for expression of CSC markers. For the first time we showed that irradiation increases histone H3K4 and H3K36 methylation in prostate cancer cells, thereby reactivating transcription of epigenetically silenced target genes. We showed that radioresistant tumor progenitor population undergoes a phenotypical switching during the course of irradiation, suggesting that controlling the phenotypical and functional properties of CSCs during radiation therapy is ultimative for the optimization of treatment strategies. Our studies have shown that CSC markers may be beneficial in prediction of tumor radiocurability, and combination of irradiation with therapies directed against CSCs can be a useful strategy to improve cancer treatment.
Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells.
Specimen part
View SamplesAim: To generate human embryonic stem cell-derived corneal endothelial cells (hESC-CECs) for transplantation in patients with corneal endothelial dystrophies.
Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.
Specimen part
View SamplesTranscriptional changes upon elicitor treatment over time (0, 30, 60 min) have been analysed with the A.thaliana Landsberg (wt) and fls2-17 (flagellin receptor mutant).
Perception of the bacterial PAMP EF-Tu by the receptor EFR restricts Agrobacterium-mediated transformation.
Age, Compound, Time
View SamplesAdult mammalian CNS neurons undergo a developmental switch in intrinsic axon growth ability associated with their failure to regenerate axons after injury. Krppel-like transcription factors (KLF) regulate intrinsic axon growth ability, but signaling regulation upstream and downstream is poorly understood. Here we find that suppressing expression of KLF9, an axon growth suppressor normally upregulated 250-fold in retinal ganglion cell (RGC) development, promotes long-distance optic nerve regeneration in vivo. We identify a novel binding partner, MAPK10/JNK3, critical for KLF9s axon growth suppressive activity. Additionally, by screening genes regulated by KLFs in RGCs, we identify dual-specificity phosphatase 14 (Dusp14) as key to limiting axon growth and regenerative ability downstream of KLF9, associated with its dephosphorylation of MAPKs critical to neurotrophic signaling of RGC axon elongation. These results now link intrinsic and extrinsic regulation of axon growth and suggest new therapeutic strategies to promote axon regeneration in the adult CNS.
The Krüppel-Like Factor Gene Target Dusp14 Regulates Axon Growth and Regeneration.
Specimen part
View SamplesSugars modulate expression of hundreds of genes in plants. Previous studies on sugar signaling, using intact plants or plant tissues, were hampered by tissue heterogeneity, uneven sugar transport and/or inter-conversions of the applied sugars. This, in turn, could obscure the identity of a specific sugar that acts as a signal affecting expression of given gene in a given tissue or cell-type. To bypass those biases, we have developed a novel biological system, based on stem-cell-like Arabidopsis suspension culture. The cells were grown in a hormone-free medium and were sustained on xylose as the only carbon source. The functional genomics approach was used to identify sugar responsive genes, which rapidly (within 1 h) respond specifically to low concentration (1 mM) of glucose, fructose and/or sucrose.
Functional dissection of sugar signals affecting gene expression in Arabidopsis thaliana.
No sample metadata fields
View SamplesRecent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma. Gene expression modules had prognostic relevance when compared with gene expression data from published melanoma samples and patient survival data. We surveyed kinome expression patterns across sub-populations of the BRAF/NRAS wild type sample and found that CDK4 and CDK2 were consistently highly expressed in the majority of cells, suggesting that these kinases might be involved in melanoma progression. Treatment of cells with the CDK4 inhibitor palbociclib restricted cell proliferation to a similar, and in some cases greater, extent than MAPK inhibitors. Finally, we identified a low abundant sub-population in this sample that highly expressed a module containing ABC transporter ABCB5, surface markers CD271 and CD133, and multiple aldehyde dehydrogenases (ALDHs), as markers for melanoma stem or initiating cells. Patient-derived cultures of the BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant metastases showed more homogeneous single-cell gene expression patterns with gene expression modules for proliferation and ABC transporters. Taken together, our results describe an intertumor and intratumor heterogeneity in melanoma short-term cultures which might be relevant for patient survival, and suggest promising targets for new treatment approaches in melanoma therapy. Overall design: RNA-seq of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively.
Pseudotime Dynamics in Melanoma Single-Cell Transcriptomes Reveals Different Mechanisms of Tumor Progression.
Specimen part, Subject
View SamplesA transcriptome-wide functional analysis of gene expression implicated multiple signaling pathways specific for Au-NP oligonucleotide complexes.
Gold nanoparticle-mediated gene delivery induces widespread changes in the expression of innate immunity genes.
Specimen part, Cell line, Treatment
View SamplesObjective: To study if diabetic and insulin-resistant states lead to mitochondrial dysfunction in the liver, or alternatively, if there is adaption of mitochondrial function to these states in the long-term range.
Liver adapts mitochondrial function to insulin resistant and diabetic states in mice.
Sex, Specimen part, Treatment
View SamplesArabipdosis thaliana (ecotype Col-0) was infected with the root pathogen Plasmodiophora brassicae. Gene expression of the host plant has been analyzed at two time points after inoculation (10 and 23 days after inoculation) compared to the correspondend control plants.
Transcriptome analysis of Arabidopsis clubroots indicate a key role for cytokinins in disease development.
Age, Specimen part, Cell line, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling of immune-competent human cells exposed to engineered zinc oxide or titanium dioxide nanoparticles.
Specimen part, Treatment, Time
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