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SRP089713
Mus musculus
67 Downloadable Samples
Illumina HiSeq 2000
Description
Mutations in the mitochondrial DNA (mtDNA) have been proposed to be essential for metabolic adaptation, and because metabolism is intrinsically associated with multiple disease states, including obesity, we hypothesized that changes in the mtDNA would significantly influence adiposity and gene expression in response to diet. To test these predictions we used Mitochondrial-Nuclear eXchange mice, which have nuclear and mitochondrial genomes that have been exchanged from different M. musculus strains. Overall design: Purpose: Mutations in the mitochondrial DNA (mtDNA) have been proposed to be essential for metabolic adaptation, and because metabolism is intrinsically associated with multiple disease states, including obesity, we hypothesized that changes in the mtDNA would significantly influence adiposity and gene expression in response to diet. To test these predictions we used Mitochondrial-Nuclear eXchange mice, which have nuclear and mitochondrial genomes that have been exchanged from different M. musculus strains. Methods: Wild type (C57BL6/J – C57n:C57mt and C3H/HeN - C3Hn:C3Hmt) and MNX (C57n:C3Hmt and C3Hn:C57mt) mouse were weaned with Chor diet and continued with Chow or changed to high-fat diet from 6 to 12-13 weeks of age. RNA samples were isolated from white adipose tissues collected from epididymal (eWAT) and inguinal (iWAT) fat, representing visceral and subcutaneous fat depots, respectively with RNeasy kit (Qiagen). Reverse transcribed cDNA libraries were sequenced with an Illumina HiSeq 2000. Read mapping was conducted with a proprietary algorithm by Expression Analysis (www.q2labsolutions.com), and read counts were used as input for differential expression analysis in DESeq2 version 1.10.1, using default settings. Results: Using an optimized data analysis workflow, we mapped about 20 million sequence reads per sample to the mouse genome (build mm9). Transcriptional changes were interrogated for 961 genes previously reported to be associated with fat metabolism and 29,209 genes representing the entire mouse transcriptome. These results show that the C57 mtDNA increased the number of DE genes in response to high fat diet in mice harboring the C3H nuclear genome (209% increase; C3Hn:C57mt versus C3Hn:C3Hmt, 165/79) and the C3H mtDNA decreased response in animals carrying the C57 nucleus (46% decrease; C57n:C3Hmt versus C57n:C57mt, 112/206) in eWAT (Figure 2B). Similarly, the high fat diet resulted in 25 and 231 DE genes in the C3Hn:C3Hmt and C3Hn:C57mt iWAT, respectively, and 344 and 143 DE genes in C57n:C57mt and C57n:C3Hmt iWAT. This corresponded to a 924% increase in the number of DE genes responding to high fat diet C3Hn:C57mt versus C3Hn:C3Hmt, and a decreased response (58% decrease) in C57n:C3Hmt relative to C57n:C57mt iWAT. Further analysis showed that each MNX and corresponding wild-type shared and had distinct DE genes in eWAT and iWAT. Conclusions: Results also show that the degree of transcriptional response influenced by the mtDNA can vary based upon the type of adipose tissue, suggesting that mtDNA background can have varying effects on the number of nuclear genes differentially responding to stimuli, depending upon tissue and location.
Publication Title
Mitochondrial - nuclear genetic interaction modulates whole body metabolism, adiposity and gene expression in vivo.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
HMCs were treated with CsA (4.2 M) for 0 12 and 48 hours. To exmaine global gene changes in the renal mesangium following CsA treatment in order to identify novel contributors to CsA-induced renal dysfunction
Publication Title
Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute renal allograft rejection is an important complication in kidney transplantation. Accurate diagnosis of rejection events is necessary for timely response and treatment. We illustrate the usefulness and biological relevance of selected multivariate approaches to detect rejection from genomic and proteomic signals. The data was used to study gene expression changes using whole genome microarray analysis of peripheral blood from subjects with acute rejection (n=20) and non-rejecting controls (n=20) to obtain insight into the molecular and biological causation of acute renal allograft rejection when combined with proteomics (iTRAQ) data for the same patients/time-points.
Publication Title
Novel multivariate methods for integration of genomics and proteomics data: applications in a kidney transplant rejection study.
Sample Metadata Fields
Sex, Specimen part, Race
View Samples- Mus musculus
- 25 Downloadable Samples
- Illumina HiSeq 4000
Description
Women suffer chronic pain more frequently than men. It is not clear whether this is due to differences in higher level cognitive processes or basic nociceptive responses. This study used a mouse model to dissociate these factors and found no differences in peripheral afferent neurons or in the spinal cord immune response to neuropathic injury. However, it did identify potential sexual dimorphisms in peripheral adaptive immune responses. Overall design: RNA-seq of naïve FACS-purified DRG neurons and MACS-purified DRG neurons after partial sciatic nerve ligation (day 8): comparison of male versus female samples
Publication Title
Sex differences in peripheral not central immune responses to pain-inducing injury.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 115 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Renal failure is characterized by important biological changes resulting in profound pleomorphic physiological effects termed uremia, whose molecular causation is not well understood. The data was used to study gene expression changes in uremia using whole genome microarray analysis of peripheral blood from subjects with end-stage renal failure (n=63) and healthy controls (n=20) to obtain insight into the molecular and biological causation of this syndrome.
Publication Title
Alteration of human blood cell transcriptome in uremia.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Race
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) <= 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.
Publication Title
White blood cell differentials enrich whole blood expression data in the context of acute cardiac allograft rejection.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
During mammalian kidney development, mesenchymal nephron progenitors (cap mesenchyme) differentiate into the epithelial cells that go on to form the nephron. Although differentiation of nephron progenitors is triggered by activation of Wnt/b-catenin signaling, constitutive activation of Wnt/b-catenin signaling blocks epithelialization of nephron progenitors. Full epithelialization of nephron progenitors requires transient activation of Wnt/b-catenin signaling. We performed transcriptional profiling of nephron progenitors responding to constitutive or transient activation of Wnt/b-catenin signaling.
Publication Title
Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 31 Downloadable Samples
- NextSeq 500
Description
To assess in vitro derived podocytes, we examined the transcriptional changes during human podocyte development and applied that knowledge to pinpoint strengths and limitations of hESC-derived podocytes. Overall design: We performed transcriptionaling profiling of kidney organoids and organoid-derived MAFB-eGFP+ podocytes at various differentiation time points.
Publication Title
In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- NextSeq 500
Description
In order to characterize and benchmark the podocytes-like cells generated through human ES cell differentiation, we generated transcriptional profiles of renal corpuscles from embryonic human kidneys using RNA-Seq. To compare, we also performed RNA-Seq of human immortalized podocyte cell lines before and after thermoswitch. Overall design: We performed RNA-Seq of poly-A selected RNA from hESC-derived kidney organoids, organoid-derived MAFB-eGFP+ podocytes at different time points, and human immortalized podocytes.
Publication Title
In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute rejection in cardiac transplant patients is still a contributing factor to limited survival of the implanted heart. Currently there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplantation acute rejection, which would be of great importance for personalizing immunosuppressive treatment. Within the Biomarkers in Transplantation initiative, the predictive biomarker discovery focused on data and samples collected before or during transplantation such as: clinical variables, genes and proteins from the recipient, and genes from the donor. Based on this study, the best predictive biomarker panel contains genes from the recipient whole blood and from donor endomyocardial tissue and has an estimated area under the curve of 0.90. This biomarker panel provides clinically relevant prediction power and may help personalize immunosuppressive treatment and frequency of rejection monitoring.
Publication Title
Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples