Samples of primary tumors collected from 23 ovarian cancer patients
Machine learning predicts individual cancer patient responses to therapeutic drugs with high accuracy.
Sex, Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits.
Specimen part, Cell line
View SamplesDuring embryogenesis, cell specification and tissue formation is directed by the concentration and temporal presentation of morphogens, and similarly, pluripotent embryonic stem cells differentiate in vitro into various phenotypes in response to morphogen treatment. Embryonic stem cells are commonly differentiated as three dimensional spheroids called embryoid bodies (EBs); however, differentiation within EBs is typically heterogeneous and disordered. Here we show that spatiotemporal control of microenvironmental cues embedded directly within EBs enhances the homogeneity, synchrony and organization of differentiation. Degradable polymer microspheres releasing retinoic acid within EBs induce the formation of cystic spheroids closely resembling the early streak mouse embryo, with an exterior of visceral endoderm enveloping an epiblast layer. These results demonstrate that controlled morphogen presentation to stem cells more efficiently directs cell differentiation and tissue formation, thereby improving developmental biology models and enabling the development of regenerative medicine therapies and cell diagnostics.
Homogeneous and organized differentiation within embryoid bodies induced by microsphere-mediated delivery of small molecules.
No sample metadata fields
View SamplesIn this study, we have utilized microarray analysis to directly compare a subset of structurally distinct, clinically relevant SERMs in the presence and absence of estradiol, using a high replicate number (10) to ensure detection of modestly regulated genes.
Research resource: Transcriptional profiling in a cellular model of breast cancer reveals functional and mechanistic differences between clinically relevant SERM and between SERM/estrogen complexes.
Cell line
View SamplesThe unprecedented magnitude of the 2013-2016 Makona Ebola virus (M-EBOV) epidemic likely resulted from multiple epidemiologic factors that set it apart from previous outbreaks. Nonetheless, genetic adaptations that distinguish M-EBOV from previous isolates may also have contributed to the scale of the epidemic. Of particular interest is a M-EBOV glycoprotein (GP) variant, GP-A82V, that was first detected at the inflection point of the 2013-2016 outbreak - when the number of cases increased exponentially - and which completely supplanted the earlier M-EBOV sequence. We found that, as compared with the earlier strain, GP-A82V increased the ability of M-EBOV to fuse with and infect cells of primate origin, including human blood dendritic cells, without altering innate immune signaling in target cells. Residue 82 is located at the NPC1-binding site on M-EBOV GP and the increased infectivity of GP-A82V was restricted to cells from species in which the NPC1 orthologue bears primate-defining residues at the critical interface. We utilized HIV-derived lentiviral vectors pseudotyped with founder and A82V containing M-EBOV GPs to explore the potential that this modification alters how human monocyte-derived dendritic cells (MDDCs) respond to EBOV GP stimulation. Overall design: We generated stocks of lentiviral vector bearing one the following three M-EBOV GPs: founder, A82V, and A82V/T230A. These viral stocks were used to challenge MDDCs from two healthy, anonymous human donors. Stimulated MDDCs were harvested at 1, 2, 4, and 6 hours after viral addition. Gene expression in M-EBOV GP challenged MDDCs was compared to a unstimulated control.
Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Functional and evolutionary significance of human microRNA seed region mutations.
Cell line
View SamplesNeural circuits in the medial entorhinal cortex (MEC) encode an animal’s position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations. Overall design: Examination of dorsal and ventral regions from 4 replicate samples each containing pooled data from 3-4 mice
Laminar and dorsoventral molecular organization of the medial entorhinal cortex revealed by large-scale anatomical analysis of gene expression.
No sample metadata fields
View SamplesLMO2 is a component of multisubunit DNA-binding transcription factor complexes that regulate gene expression in hematopoietic stem and progenitor cell development. Enforced expression of LMO2 causes leukemia by inducing hematopoietic stem cell-like features in T-cell progenitor cells, but the biochemical mechanisms of LMO2 function have not been fully elucidated. In this study we systematically dissected the LMO2/LDB1 binding interface to investigate the role of this interaction in T-cell leukemia. Alanine scanning mutagenesis of the LIM interaction domain of LDB1 revealed a discrete motif R320LITR required for LMO2 binding. Most strikingly, co-expression of full length, wild type LDB1 increased LMO2 steady state abundance, whereas co-expression of mutant proteins deficient in LMO2 binding compromised LMO2 stability. These mutant LDB1 proteins also exerted dominant negative effects on growth and transcription in diverse leukemic cell lines. Raw gene expression data on HSB-2 cells is presented here. Overall design: RNAseq were performed on HSB cell lines to examine their expression patterns
LMO2 Oncoprotein Stability in T-Cell Leukemia Requires Direct LDB1 Binding.
No sample metadata fields
View SamplesMicroRNAs (miRNAs) are small non-coding RNAs that play a central role in the regulation of gene expression at the post transcriptional and/or translational level thus impacting various biological processes. Dysregulation of miRNAs could affect processes associated with progression of a variety of diseases including cancer. Majority of miRNA targeting in animals involves a 7-nt seed region mapping to positions 2-8 at the molecules 5' end. The importance of this 7 nt sequence to miRNA function is evidenced by the fact that the seed region sequence of many miRNAs is highly conserved within and between species. In this study, we computationally and experimentally explore the functional significance of sequence variation within the seed region of human miRNAs. Our results indicate that change of a single nt within the 7-nt seed region changes the spectrum of targeted mRNAs significantly meanwhile further nt changes have little to no additional effect. This high functional cost of even a single nucleotide change within the seed region of miRNAs explains why the seed sequence is highly conserved among many miRNA families both within and between species and could help clarify the likely mechanisms underlying the evolution of miRNA regulatory control.
Functional and evolutionary significance of human microRNA seed region mutations.
Cell line
View SamplesMicroRNAs (miRNAs) are small non-coding RNAs that play a central role in the regulation of gene expression at the post transcriptional and/or translational level thus impacting various biological processes. Dysregulation of miRNAs could affect processes associated with progression of a variety of diseases including cancer. Majority of miRNA targeting in animals involves a 7-nt seed region mapping to positions 2-8 at the molecules 5' end. The importance of this 7 nt sequence to miRNA function is evidenced by the fact that the seed region sequence of many miRNAs is highly conserved within and between species. In this study, we computationally and experimentally explore the functional significance of sequence variation within the seed region of human miRNAs. Our results indicate that change of a single nt within the 7-nt seed region changes the spectrum of targeted mRNAs significantly meanwhile further nt changes have little to no additional effect. This high functional cost of even a single nucleotide change within the seed region of miRNAs explains why the seed sequence is highly conserved among many miRNA families both within and between species and could help clarify the likely mechanisms underlying the evolution of miRNA regulatory control.
Functional and evolutionary significance of human microRNA seed region mutations.
Cell line
View Samples