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SRP116949
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
Surfactant deficiency, diffuse alveolar damage and respiratory failure caused by loss of Abca3 in AT2 cells was followed by remarkable proliferation of alveolar cells and selective survival of ABCA3 sufficient cells resulting in regeneration of alveolar structure and function, providing the conceptual framework for the development of therapies to ameliorate lung diseases caused by mutations in ABCA3 and other genes critical for AT2 cell function or surfactant homeostasis. Overall design: Control and Abca3 cKO AT2 cell RNA-seq at 6 days post tamoxifen in adult mice.
Publication Title
Alveolar injury and regeneration following deletion of ABCA3.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
We investigated the ability of monoclonal B cells to restore primary and secondary antibody responses in adoptive immune-deficient hosts. Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM+IgG- and IgM-IgG+ antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division. Using RNA sequencing, we compared the gene expression profil of memory B cells subpopulations and activated B cells. These data showed a clear discrimination of naïve and activated/memory cells while indicating only minor differences between both subsets of memory cells. Overall design: mRNA profiles of B cell subtypes (activated, memory IgM+, memory IgG+) were generated by deep sequencing, in triplicate, using Illumina
Publication Title
Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 27 Downloadable Samples
- Illumina HiSeq 2500
Description
Mammalian fetal lung development is a complex biological process.Despite considerable progress, a comprehensive understanding of the dynamic regulatory networks that govern postnatal alveolar lung development is still lacking. The purpose of this study as part of the LungMAP consortium (www.lungmap.net) is to understand the transcriptional changes in the process of mammalian lung development. Overall design: Method: We isolated alveolar septa from c57BL/6 mice by laser capture microdissection from 14 time points (E16.5, P0.5, P1, P1.5, P2.5, P4, P5, P7, P10, P13.5, P15, P19, P23, and P28) and performed RNA-Sequencing by Illumina Hi-Seq 2500 .
Publication Title
LungMAP: The Molecular Atlas of Lung Development Program.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Macaca mulatta, Mus caroli, Mus musculus, Pan troglodytes, Pongo pygmaeus, Homo sapiens, Mus spretus
- 13 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2), Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Microarray technologies allow the identification of large numbers of expression differences within and between species. Although environmental and physiological stimuli are clearly responsible for changes in the expression levels of many genes, it is not known whether the majority of changes of gene expression fixed during evolution between species and between various tissues within a species are caused by Darwinian selection or by stochastic processes. We find the following: (1) expression differences between species accumulate approximately linearly with time; (2) gene expression variation among individuals within a species correlates positively with expression divergence between species; (3) rates of expression divergence between species do not differ significantly between intact genes and expressed pseudogenes; (4) expression differences between brain regions within a species have accumulated approximately linearly with time since these regions emerged during evolution. These results suggest that the majority of expression differences observed between species are selectively neutral or nearly neutral and likely to be of little or no functional significance. Therefore, the identification of gene expression differences between species fixed by selection should be based on null hypotheses assuming functional neutrality. Furthermore, it may be possible to apply a molecular clock based on expression differences to infer the evolutionary history of tissues.
Publication Title
A neutral model of transcriptome evolution.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Sus scrofa
- 12 Downloadable Samples
- Porcine Gene 1.0 ST Array (porgene10st)
Description
Expression data from valvular interstitial cells cultured in 2D or 3D PEG hydrogel systems compared to culture on tissue culture polystyrene and freshly isolated cells
Publication Title
Transcriptional profiles of valvular interstitial cells cultured on tissue culture polystyrene, on 2D hydrogels, or within 3D hydrogels.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Establishment of human iPSC-based models for the study and targeting of glioma initiating cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gliomas can originate upon transformation of adult Neural Progenitor Cells (NPCs) to Tumor Initiating Cells (TICs). Studies on human Glioma TICs (GTICs) have focused on the use of primary tumors from which GTICs could be isolated. Therefore investigations on the driver events underlying NPC transformation and human glioma initiation remain limited to the use of human embryonic material. Here we report on the development of strategies for the modeling of human gliomagenesis based on the use of human induced Pluripotent Stem Cells (hiPSCs). Transformation of hiPSC-derived NPCs (iNPCs) by defined genetic alterations led to the establishment of tractable human GTIC models suitable for studying the early steps of gliomagenesis as well as for screening studies. Dysregulation of PI3K, MAPK and p53 signaling in iNPCs led to the acquisition of functional GTIC properties. In vivo transplantation led to the formation of highly aggressive, infiltrative and heterogeneous tumors upon limited dilutions and secondary transplantation, faithfully recapitulating gliomagenesis. Metabolic modulation by chemical approaches compromised GTIC viability. Pilot screening of 101 anti-cancer compounds identified 3 molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results demonstrate the potential of hiPSCs for the functional testing of putative driver mutations underlying human tumorigenesis and pave new avenues for the development of personalized cancer therapeutics.
Publication Title
Establishment of human iPSC-based models for the study and targeting of glioma initiating cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1R132H in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced -ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased.Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells over-expressed Wnt, cell cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1R132H mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis. Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1R132H in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced -ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells over-expressed Wnt, cell cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1R132H mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.
Publication Title
Expression of Idh1<sup>R132H</sup> in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Saccharomyces cerevisiae
- 33 Downloadable Samples
- Illumina HiSeq 2000
Description
During transcription initiation, the TFIIH-kinase Kin28/Cdk7 marks RNA polymerase II (Pol II) by phosphorylating the C-terminal domain (CTD) of its largest subunit. Here we describe a structure-guided chemical approach to covalently and specifically inactivate Kin28 kinase activity in vivo. This method of irreversible inactivation recapitulates both the lethal phenotype and the key molecular signatures that result from genetically disrupting Kin28 function in vivo. Inactivating Kin28 impacts promoter release to differing degrees and reveals a “checkpoint” during the transition to productive elongation. While promoter-proximal pausing is not observed in budding yeast, inhibition of Kin28 attenuates elongation-licensing signals, resulting in Pol II accumulation at the +2 nucleosome and reduced transition to productive elongation. Furthermore, upon inhibition, global stabilization of mRNA masks different degrees of reduction in nascent transcription. This study resolves long-standing controversies on the role of Kin28 in transcription and provides a rational approach to irreversibly inhibit other kinases in vivo. Overall design: Total RNA was collected from wild-type and analog-sensitive Kin28 strains treated with reversible inhibitor 1-NAPP-1, irreversible inhibitor CMK, and solvent control DMSO. Equivalent ratios of S. pombe : S. cerevisiae cells were added to each sample before RNA extraction for normalization of read counts after sequencing. Nascent RNA was purified from total RNA by 4-thiouracil labeling, biotinylation, and streptavidin-pulldown. As a negative control, nascent RNA was also extracted from total RNA from cells that had not been treated with 4-thiouracil.
Publication Title
Engineered Covalent Inactivation of TFIIH-Kinase Reveals an Elongation Checkpoint and Results in Widespread mRNA Stabilization.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In order to elucidate the molecular mechanism giving rise to the rare In(Lu) type of Lu(a-b-) blood group phenotype we compared the transcriptome of normal and In(Lu) erythroblasts at different stages of maturation. Many erythroid-specific genes had reduced transcript levels suggesting the phenotype resulted from a transcription factor abnormality. A search for mutations in erythroid transcription factors revealed mutations in the promoter or coding sequence of EKLF in 21 of 24 individuals with the In(Lu) phenotype. In all cases the mutant EKLF allele occurred in the presence of a normal EKLF allele. Individuals with the In(Lu) phenotype have no reported pathology indicating that one functional EKLF allele is sufficient to sustain human erythropoiesis. These data provide the first description of inactivating mutations in human EKLF and the first demonstration of a blood group phenotype resulting from mutations in a transcription factor.
Publication Title
Mutations in EKLF/KLF1 form the molecular basis of the rare blood group In(Lu) phenotype.
Sample Metadata Fields
No sample metadata fields
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