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SRP179668
Homo sapiens
8 Downloadable Samples
Illumina HiSeq 4000
Description
Red blood cells (RBCs) mature within a specialized niche (the erythroblastic island (EI)), which consists of a central macrophage surrounded by differentiating erythroblasts. Human Induced Pluripotent Stem Cell derived macrophages (iPSC-DMs) enhance proliferation and terminal maturation of Umbilical Cord Blood (UCB) CD34+ derived erythroid cells and iPSC derived erythroid cells. These effects are further increased when an inducible KLF1-ERT2 fusion protein is activated in iPSC-DMs. To assess the mechanism of action, we sought to compare the transcriptome of iPSC-DMs with and without KLF1 activation. For this, we used an inducible IPSC line (iKLF1.2) in which upon tamoxifen addition, the KLF1 transcription factor is translocated to nucleus and consequently KLF1 downstream targets are expressed. The identification and characterisation of could identify factors involved in erythroid maturation and thus helpful to improve current protocols to manufacture RBCs in vitro. Overall design: iKLF1.2 iPSCs were differentiated to macrophages and then split into 2 groups, one was treated with tamoxifen for the last 4 days of culture to activate KLF1. The other group was not treated with tamoxifen. Four biologically independent differentiation experiments were carried out and so 8 samples were generated: 4 samples of untreated iKLF1.2 iPSCs-derived macrophages and 4 samples of tamoxifen treated iKLF1.2 iPSC-derived macrophages. Total RNA was extracted from each sample and RNA integrity was of a high enough quality for library preparation, as all RIN values were above 9 for every sample.
Publication Title
Genetic programming of macrophages generates an in vitro model for the human erythroid island niche.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Rattus norvegicus
- 54 Downloadable Samples
Affymetrix Rat Expression 230A Array (rae230a)
Description
The Long Evans/orl (LE/orl) rat is an animal model of inherited undescended testis (UDT). To explore genetic mechanisms of UDT, we studied differential gene expression in LE/orl and LE wild type (LE/wt) fetal gubernaculum and testis.
Publication Title
Altered expression of muscle- and cytoskeleton-related genes in a rat strain with inherited cryptorchidism.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 17 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Insl3 is a testis-derived hormone that induces growth and differentiation of the fetal gubernaculum. The goal of this study was to identify genes showing altered expression in fetal gubernaculum following Insl3 exposure.
Publication Title
Insulin-like 3 exposure of the fetal rat gubernaculum modulates expression of genes involved in neural pathways.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 758 Downloadable Samples
- Illumina HiSeq 2500
Description
Genetic variation modulating risk of sporadic Parkinson's disease (PD) has been primarily explored through genome wide association studies (GWAS). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal timepoints. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a novel postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including known PD genes and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1 null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research. Overall design: 473 single cell RNA-Seq samples from sorted mouse Th-eGFP+ dopaminergic neurons collected at two timepoints from three distinct brain regions.
Publication Title
Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 80 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The goal of this study was to identify candidate genes that may influence alcohol consumption by comparing gene expression in 5 brain regions of alcohol-nave iP and P.NP rats.
Publication Title
Candidate genes for alcohol preference identified by expression profiling in alcohol-preferring and -nonpreferring reciprocal congenic rats.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 60 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
A highly significant quantitative trait locus (QTL) that influenced alcohol preference was identified in the iP/iNP rats on chromosome 4.
Publication Title
Identification of candidate genes for alcohol preference by expression profiling of congenic rat strains.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Proximal spinal muscular atrophy (SMA) is an early onset, autosomal recessive motor neuron disease caused by loss of or mutation in SMN1 (survival motor neuron 1). Despite understanding the genetic basis underlying this disease, it is still not known why motor neurons (MNs) are selectively affected by the loss of the ubiquitously expressed SMN protein. Using a mouse embryonic stem cell (mESC) model for severe SMA, the RNA transcript profiles (transcriptomes) between control and severe SMA (SMN2+/+;mSmn-/-) mESC-derived MNs were compared in this study using massively parallel RNA sequencing (RNA-Seq). The MN differentiation efficiencies between control and severe SMA mESCs were similar. RNA-Seq analysis identified 3094 upregulated and 6964 downregulated transcripts in SMA mESC-derived MNs when compared against control cells. Pathway and network analysis of the differentially expressed RNA transcripts showed that pluripotency and cell proliferation transcripts were significantly increased in SMA MNs while transcripts related to neuronal development and activity were reduced. The differential expression of selected transcripts such as Crabp1, Crabp2 and Nkx2.2 was validated in a second mESC model for SMA as well as in the spinal cords of low copy SMN2 severe SMA mice. Furthermore, the levels of these selected transcripts were restored in high copy SMN2 rescue mouse spinal cords when compared against low copy SMN2 severe SMA mice. These findings suggest that SMN deficiency affects processes critical for normal development and maintenance of MNs. Overall design: RNA profiles were generated from FACS-purified control and SMA mESC-derived motor neurons (n=3/genotype) by deep sequencing using Illumina HighSeq 2500
Publication Title
Transcriptome profiling of spinal muscular atrophy motor neurons derived from mouse embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 26 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This study was designed to provide additional insight into testicular hormone production and responsiveness in the orl strain and complement ongoing efforts to characterize the genetic basis of cryptorchidism in this isolated rat colony.
Publication Title
Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Topoisomerase 1 (TOP1) poisons like camptothecin (CPT), which are used as chemotherapeutic agents in cancer, elicit DNA damage in quiescient neurons. In this study, we examined the effects of CPT and actinomycin D (ActD) on neuronal cells. Motor (MNs) and cortical (CNs) neurons were more susceptible to the toxic effects of CPT and ActD than fibroblasts. MNs and CNs exhibited a delayed DNA damage responseincrease in nuclear -H2AX focirelative to fibroblasts. Neuronal cells expressed higher levels of Top1 mRNA than fibroblasts which could explain their enhanced vulnerability to CPT and ActD toxicity. Microarray analysis was performed to identify differentially regulated transcripts in MNs treated with CPT for 2 hours. Many immediate-early genes including Fos and Egr-1 were upregulated in CPT-treated MNs. Fos mRNA levels were elevated in all cells types treated with CPT; Egr-1 transcript levels, however, were reduced in CPT-treated fibroblasts even though they were elevated in treated MNs and CNs. Pathway and network analysis of the differentially expressed transcripts revealed activation of ERK and JNK signaling cascades in CPT-treated MNs. In conclusion, MNs were more vulnerable than fibroblasts to the damaging effects of TOP1 poisons and they elicit a unique intracellular response to CPT treatment.
Publication Title
Identification of early gene expression changes in primary cultured neurons treated with topoisomerase I poisons.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Infection is a major complication and cause of mortality and morbidity after acute stroke however the mechanisms are poorly understood. After experimental stroke the microarchitecture and cellular composition of the spleen are extensively disrupted resulting in deficits to immune function.
Publication Title
Experimental Stroke Differentially Affects Discrete Subpopulations of Splenic Macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples