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SRP103116
Mus musculus
18 Downloadable Samples
Illumina HiSeq 2500
Description
Oligodendrocyte dysfunction underlies many neurological disorders but rapid assessment of mutation-specific effects in these cells has been impractical. To enable functional genetics in oligodendrocytes, here we report a highly efficient method for generating oligodendrocytes and their progenitors from mouse embryonic and induced pluripotent stem cells, independent of mouse strain or mutational status. We demonstrate that this approach, when combined with genome engineering, provides a powerful platform for the expeditious study of genotype-phenotype relationships in oligodendrocytes. Overall design: Cells were lysed directly in 1 ml of TRIzol (Thermo Fisher) and stored at -80°C. Once all samples were collected, samples were thawed on ice and RNA was separated with chloroform using Phase Lock Gel tubes (5prime). RNA was isolated using the miRNeasy Mini Kit (Qiagen) according to the manufacture's protocol. One microgram of each sample was then subject to ribosome depletion, fragmented, and library prepared using the TruSeq Stranded Total RNA Kit with Ribo Zero Gold (Illumina) according to the manufacturer's protocol and indexed using TruSeq adapters. One hundred base pair paired-end reads were generated for each sample on the Illumina HiSeq 2500 (Case Western Reserve University Sequencing Core; Cleveland, OH). Samples include mESC derived oligodendrocyte progenitor cells (OPCs) from four different wildtype mouse strains at 0 hr, 24, hr, 48 hr, and 72 hr after treatment with thyroid hormone T3 (n = 4 biological replicates per time point). Two additional samples include mutant OPCs (shiverer and MYRF knockout ''delMYRF'') at 72 hr time point.
Publication Title
Rapid functional genetics of the oligodendrocyte lineage using pluripotent stem cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
Description
Organoid technologies provide an accessible system in which to examine the generation, self-organization,and 3-dimensional cellular interactions during development of the human cerebral cortex. However, oligodendrocytes, the myelinating glia of the central nervous system and third major neural cell type, are conspicuously absent from current protocols. Here we reproducibly generate human oligodendrocytes and myelin in pluripotent stem cell-derived cortical spheroids. Transcriptional and immunohistochemical analysis of the spheroids demonstrates molecular features consistent with maturing human oligodendrocytes within 14 weeks of culture, including expression of MyRF, PLP1, and MBP proteins. Histological analysis by electron microscopy shows initial wrapping of human neuronal axons with myelin by 20 weeks and maturation to compact myelin by 30 weeks in culture. Treatment of spheroids with previously identified promyelinating drugs enhances the rate and extent of human oligodendrocyte generation and myelination. Furthermore, generation of spheroids from patients with a severe genetic myelin disorder, Pelizaeus-Merzbacher disease, demonstrates the ability to recapitulate human disease phenotypes, which were in turn improved with both pharmacologic and CRISPR-based approaches. Collectively, these 3-dimensional, multi-lineage cortical spheroids provide a versatile platform to observe and perturb the complex cellular interactions that occur during developmental myelination of the brain and offer new opportunities for disease modeling and therapeutic development in human tissue. Overall design: RNAseq profiles comparing neuro-cortical spheroids and oligo-cortical spheroids
Publication Title
Induction of myelinating oligodendrocytes in human cortical spheroids.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 47 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Although a number of animal model studies have addressed changes in gene expression in the parenchyma and their relationship to emphysema, much less is known about the pathogenesis of cigarette smoke-induced small airway remodeling. In this study, we exposed rat tracheal explants to whole smoke for 15 minutes, and then cultured the explants in air. The airway transcriptome was evaluated using RAE 230_2 GeneChips. By 2 hours after starting smoke exposure, expression levels of 502 genes were changed up or down by more than 1.5 times (p values <0.01 or less), and by 24 hours, 1870 genes were significantly changed up or down. These included genes involved in anti-oxidant protection, epithelial defense and remodeling, inflammatory mediators and transcription factors, and a number of unexpected genes including the MMP-12 inducer, tachykinin-1 (substance P). Pre-treatment of the explants with 1 x 10-7 M dexamethasone reduced the number of significantly changed genes by approximately 47% at 2 hr and 68% at 24 hours, and in almost all instances, reduced the magnitude of the smoke-induced changes. We conclude that even a very brief exposure to cigarette smoke can lead to rapid changes in the expression of a large number of genes in rat tracheal explants, and that these effects are directly mediated by smoke, without a need for exogenous inflammatory cells. Steroids, contrary to the usual belief, are able to ameliorate many of these changes, at least in this very acute model.
Publication Title
Modification of the rat airway explant transcriptome by cigarette smoke.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene-environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlation of latitude, summer daylight exposure (SDE) was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene-environment interactions in children treated with r-hGH.
Publication Title
Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.
Sample Metadata Fields
Sex, Age
View Samples- Gallus gallus
- 10 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The study is relevant to an understanding of the forces that lead to sex differences in the brain and other somatic tissues. Many neural and psychiatric diseases affect men and women differently, so the understanding of sex differences in brain function impacts on our understanding of why the male and female brain differ in their susceptibility to disease.
Publication Title
Sex bias and dosage compensation in the zebra finch versus chicken genomes: general and specialized patterns among birds.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 10 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The study is relevant to an understanding of the forces that lead to sex differences in the brain. Many neural and psychiatric diseases affect men and women differently, so the understanding of sex differences in brain function impacts on our understanding of why the male and female brain differ in their susceptibility to disease.
Publication Title
Sex bias and dosage compensation in the zebra finch versus chicken genomes: general and specialized patterns among birds.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 9 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The study is relevant to an understanding of the forces that lead to sex differences in the brain. Many neural and psychiatric diseases affect men and women differently, so the understanding of sex differences in brain function impacts on our understanding of why the male and female brain differ in their susceptibility to disease.
Publication Title
Sex bias and dosage compensation in the zebra finch versus chicken genomes: general and specialized patterns among birds.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Samples of primary tumors collected from 23 ovarian cancer patients
Publication Title
Machine learning predicts individual cancer patient responses to therapeutic drugs with high accuracy.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
T cell development relies on the precise developmental control of various cellular functions for appropriate positive and negative selection. Previously, gene expression profiling of peptide-driven negative selection events in the N15 TCR class I MHC-restricted mouse and D011.10 TCR class II MHC-restricted mouse has offered insights into the coordinate engagement of biological processes affecting thymocyte development. However, there has been little comparable detailed in vivo global genome expression analysis reported for positive selection.
Publication Title
PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 19 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
A recent two-year NTP cancer bioassay showed a marked increase in the incidence of malignant mesothelioma arising from the tunica vaginalis in male Fischer 344/N rats exposed to Vinylidene chloride (VDC). Aged male F344/N rats are prone to developing spontaneous peritoneal mesotheliomas, which also arise predominantly from the tunica vaginalis of the testes. A definitive mechanism for the observed increased incidence in VDC-exposed rats is unknown. Investigation of the molecular alterations that occur in mesotheliomas from vehicle control and VDC-exposed rats may provide insight into their pathogenesis, as well enable a better understanding regarding the mechanisms underlying chemically induced mesothelioma in rodents. Mesothelial cell function represents a complex interplay of pathways related to host defense mechanisms and maintenance of cellular homeostasis. Global gene expression profiles of spontaneous mesotheliomas from vehicle control male F344/N rats from various two-year National Toxicology Program carcinogenicity bioassays were compared to mesotheliomas from VDC-exposed rats to characterize the molecular features that are present in mesotheliomas from VDC-exposed animals, and to elucidate tumor-specific gene expression profiles. The resulting gene expression pattern showed that mesotheliomas from VDC-exposed animals are genomically very different from spontaneous tumors; while both tumor types are characterized by alterations in gene expression associated with carcinogenic pathways (oncogenes, tumor suppressor genes, growth factors, etc.), mesotheliomas from VDC-exposed animals are associated with increased dysreguation of immune pathways and inflammatory mediators. Alterations in these pathways may suggest a pro-inflammatory and immune dysfunction signature as one mechanism in the observed increased incidence of these tumors in VDC-exposed animals.
Publication Title
Spontaneous mesotheliomas in F344/N rats are characterized by dysregulation of cellular growth and immune function pathways.
Sample Metadata Fields
Disease
View Samples