Gene expression profiling of surgical biopsies from 74 breast cancer patients of different subtypes from Hamburg dataset.
Prognostic relevance of glycosylation-associated genes in breast cancer.
Sex, Specimen part
View SamplesAnalysis of differences in gene expression between different cell types of the vascular niche. Looking for candidates, that could potentially be up-or downregualted in the different cell types
Pericyte-expressed Tie2 controls angiogenesis and vessel maturation.
Specimen part
View SamplesThe final size of plant organs such as leaves is tightly controlled by environmental and genetic factors that must spatially and temporally coordinate cell expansion and cell cycle activity. However this regulation of organ growth is still poorly understood. The aim of this study is to gain more insight in the genetic control of leaf size in Arabidopsis by performing a comparative analysis of transgenic lines that produce larger leaves under standardized environmental conditions. To this end, we selected five genes, belonging to different functional classes, that all positively affect leaf size when over-expressed: AVP1, GRF5, JAW, BRI1 and GA20OX1. We show that the increase in leaf area in these lines depends on leaf position and growth conditions and that all five lines affect leaf size differently. However, in all cases an increase in cell number is, entirely or predominantly, responsible for the leaf size enlargement. By means of analyses of hormone levels, transcriptome and metabolome we provide deeper insight in the molecular basis of the growth phenotype for the individual lines. A comparative analysis between them indicates that enhanced organ growth is governed by different, seemingly independent pathways. The analysis of transgenic lines simultaneously over-expressing two growth-enhancing genes further supports the concept that multiple pathways independently converge on organ size control in Arabidopsis.
Increased leaf size: different means to an end.
Specimen part
View SamplesCurrent preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and human tumors in preclinical drug testing. Besides 3D growth, it is also advantageous to simulate shear stress, compound flux and removal of metabolites, e.g. via bioreactor systems, through which culture medium is constantly pumped at a flow rate reflecting physiological conditions. Here, we show that both Staticic 3D growth and 3D growth within a bioreactor system modulate key hallmarks of cancer cells, including proliferation and cell death as well as macroautophagy, a recycling pathway often activated by highly proliferative tumors to cope with metabolic stress. The autophagy-related gene expression profiles of 2D- and 3D-grown cells are substantially different, with the 3D-grown cells exhibiting an expression profile closely resembling the (patho-) physiological Statice of a tumor. Underscoring the importance of this pathway, autophagy-controlling transcription factors, such as TFEB and FOXO3, are upregulated in tumors, and 3D-grown cells have increased expression compared with cells grown in 2D conditions. Three-dimensional cultures depleted of the autophagy mediators BECN1, ATG5 or ATG7 or the transcription factor FOXO3, are more sensitive to cytotoxic treatment. Accordingly, combining cytotoxic treatment with compounds affecting late autophagic flux, such as chloroquine, renders the 3D-grown cells more susceptible to therapy and increases intracellular doxorubicin concentration to the level of 2D-grown cells. Altogether, 3D cultures are a valuable tool to study drug response of tumor cells, as these models recapitulate (patho-) physiologically relevant pathways, such as autophagy.
Three-dimensional tumor cell growth stimulates autophagic flux and recapitulates chemotherapy resistance.
Specimen part, Cell line
View SamplesThe final size of plant organs such as leaves is tightly controlled by environmental and genetic factors that must spatially and temporally coordinate cell expansion and cell cycle activity. However this regulation of organ growth is still poorly understood. The aim of this study is to gain more insight in the genetic control of leaf size in Arabidopsis by performing a comparative analysis of transgenic lines that produce larger leaves under standardized environmental conditions. To this end, we selected five genes, belonging to different functional classes, that all positively affect leaf size when over-expressed: AVP1, GRF5, JAW, BRI1 and GA20OX1. We show that the increase in leaf area in these lines depends on leaf position and growth conditions and that all five lines affect leaf size differently. However, in all cases an increase in cell number is, entirely or predominantly, responsible for the leaf size enlargement. By means of analyses of hormone levels, transcriptome and metabolome we provide deeper insight in the molecular basis of the growth phenotype for the individual lines. A comparative analysis between them indicates that enhanced organ growth is governed by different, seemingly independent pathways. The analysis of transgenic lines simultaneously over-expressing two growth-enhancing genes further supports the concept that multiple pathways independently converge on organ size control in Arabidopsis.
Increased leaf size: different means to an end.
Specimen part
View SamplesThe final size of plant organs such as leaves is tightly controlled by environmental and genetic factors that must spatially and temporally coordinate cell expansion and cell cycle activity. However this regulation of organ growth is still poorly understood. The aim of this study is to gain more insight in the genetic control of leaf size in Arabidopsis by performing a comparative analysis of transgenic lines that produce larger leaves under standardized environmental conditions. To this end, we selected five genes, belonging to different functional classes, that all positively affect leaf size when over-expressed: AVP1, GRF5, JAW, BRI1 and GA20OX1. We show that the increase in leaf area in these lines depends on leaf position and growth conditions and that all five lines affect leaf size differently. However, in all cases an increase in cell number is, entirely or predominantly, responsible for the leaf size enlargement. By means of analyses of hormone levels, transcriptome and metabolome we provide deeper insight in the molecular basis of the growth phenotype for the individual lines. A comparative analysis between them indicates that enhanced organ growth is governed by different, seemingly independent pathways. The analysis of transgenic lines simultaneously over-expressing two growth-enhancing genes further supports the concept that multiple pathways independently converge on organ size control in Arabidopsis.
Increased leaf size: different means to an end.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.
Cell line
View SamplesThe final size of plant organs such as leaves is tightly controlled by environmental and genetic factors that must spatially and temporally coordinate cell expansion and cell cycle activity. However this regulation of organ growth is still poorly understood. The aim of this study is to gain more insight in the genetic control of leaf size in Arabidopsis by performing a comparative analysis of transgenic lines that produce larger leaves under standardized environmental conditions. To this end, we selected five genes, belonging to different functional classes, that all positively affect leaf size when over-expressed: AVP1, GRF5, JAW, BRI1 and GA20OX1. We show that the increase in leaf area in these lines depends on leaf position and growth conditions and that all five lines affect leaf size differently. However, in all cases an increase in cell number is, entirely or predominantly, responsible for the leaf size enlargement. By means of analyses of hormone levels, transcriptome and metabolome we provide deeper insight in the molecular basis of the growth phenotype for the individual lines. A comparative analysis between them indicates that enhanced organ growth is governed by different, seemingly independent pathways. The analysis of transgenic lines simultaneously over-expressing two growth-enhancing genes further supports the concept that multiple pathways independently converge on organ size control in Arabidopsis.
Increased leaf size: different means to an end.
Specimen part
View SamplesMedulloblastoma (MB) is the most common malignant primary pediatric brain cancer. Among the most aggressive subtypes, Group 3 and Group 4 originate from stem/progenitor cells, frequently metastasize, and often display the worst prognosis, yet, as the names imply, we know the least about the molecular mechanisms driving their progression. Here, we show that the transcription factor orthodenticle homeobox 2 (OTX2) promotes self-renewal while inhibiting differentiation in vitro and increases tumor-initiating capacity from MB stem cell populations in vivo. Characterization of the OTX2 regulatory network revealed a novel relationship between OTX2 and genes associated with multiple axon guidance signaling pathways in Group 3 and Group 4 MB stem/progenitor cells. In particular, OTX2 levels were negatively correlated with semaphorin (SEMA) signaling, as expression of 9 SEMA pathway genes is upregulated following OTX2 knockdown with some being potential direct OTX2 targets. Importantly, this negative correlation between OTX2 and SEMA pathway genes was also observed in patient samples, with lower expression of SEMA4D associated with poor outcome in Group 3 and 4 tumors. Functional studies using established and newly derived MB cell lines demonstrated that increased levels of SEMA pathway genes are associated with decreased self-renewal and growth, and that RHO signaling, known to mediate the effects of SEMA genes, is contributing to the OTX2 KD phenotype. Our study provides critical mechanistic insight into the networks controlled by OTX2 in self-renewing MB cells and reveals novel roles for axon guidance genes and their downstream effectors as putative tumor suppressors and therapeutic targets in Group 3 and Group 4 MB.
Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences.
Specimen part, Disease, Treatment
View Samples