This SuperSeries is composed of the SubSeries listed below.
Disruption of histone methylation in developing sperm impairs offspring health transgenerationally.
Specimen part
View SamplesA fathers lifetime experiences can be transmitted to his offspring to affect
Disruption of histone methylation in developing sperm impairs offspring health transgenerationally.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesGlobal microarray (HG U133 Plus 2.0) was used to investigate the effects of resistance exercise and resistance training on the skeletal muscle transcriptome profile of 28 young and old adults. Vastus lateralis muscle biopsies were obtained pre and 4hrs post resistance exercise in the beginning (untrained state) and at the end (trained state) of a 12 wk progressive resistance training program.
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sex, Specimen part, Time
View SamplesGlobal microarray (HG U133 Plus 2.0) was used for the first time to investigate the effects of resistance exercise on the transcriptome in slow-twitch myosin heavy chain (MHC) I and fast-twitch MHC IIa muscle fibers of young and old women. Vastus lateralis muscle biopsies were obtained pre and 4hrs post resistance exercise in the beginning (untrained state) and at the end (trained state) of a 12 wk progressive resistance training program.
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sex, Specimen part, Subject, Time
View SamplesGlobal microarray (HG U133 Plus 2.0) was used to investigate the basal level skeletal muscle transcriptome profile of young and old adults. One vastus lateralis muscle biopsy was obtained in the basal state from 36 different subjects.
Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.
Sex, Specimen part
View SamplesAs part of a larger effort to provide proof-of-concept in vitro only risk assessments, we have developed a suite of high throughput assays for key readouts in the p53 DNA damage response toxicity pathway: DSB DNA damage (p-H2AX), permanent chromosomal damage (micronuclei; MN), p53 activation, p53 transcriptional activity, and cell fate (cell cycle arrest, apoptosis,MN). Dose-response studies were performed with these protein and cell fate assays, together with whole genome transcriptomics, for three prototype chemicals: etoposide (ETP), quercetin (QUE) and methyl methanesulfonate (MMS). Data were collected in a human cell line expressing wild-type p53 (HT1080) and results were confirmed in a second p53 competent cell line (HCT 116). At chemical concentrations causing similar increases in p53 protein expression, p53-mediated protein expression and cellular processes showed substantial chemical-specific differences. These chemical-specific differences in the p53 transcriptional response appear to be determined by augmentation of the p53 response by co-regulators. More importantly, dose-response data for each of the chemicals indicates that the p53 transcriptional response does not prevent MN induction at low concentrations. In fact, the no observed effect levels (NOELs) and benchmark doses (BMDs) for MN induction were less than or equal to those for p53-mediated gene transcription regardless of the test chemical, indicating that p53s post-translational responses may be more important than transcriptional activation in the response to low dose DNA damage. This effort demonstrates the process of defining key assays required for a pathway-based, in vitro-only risk assessment, using the p53-mediated DNA damage response pathway as a prototype.
Profiling dose-dependent activation of p53-mediated signaling pathways by chemicals with distinct mechanisms of DNA damage.
Specimen part, Cell line
View SamplesAscending aortic aneurysms (AscAA) are a life-threatening disease whose molecular basis is poorly understood. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV), which is associated with AscAA. Here, we describe a novel role for Notch1 in AscAA. We found that Notch1 haploinsufficiency exacerbated the aneurysmal aortic root dilation seen in the Marfan syndrome mouse model and that heterozygous deletion of Notch1 in the second heart field (SHF) lineage recapitulated this exacerbated phenotype. Lineage tracing analysis showed that loss of Notch1 in the SHF reduces the number of SHF-derived smooth muscle cells in the aortic root, and RNA-seq analysis demonstrated distinct in vivo expression patterns between lineage-specific regions of the ascending aorta. Finally, Notch1+/- mice in a predominantly 129S6 background develop aortic root dilation, indicating that loss of Notch1 independently predisposes to AscAA. These findings are the first to demonstrate a SHF lineage-specific role for Notch1 in AscAA and suggest that genes linked to the development of BAV may also contribute to the associated aortopathy. Overall design: To determine why dilation was localized to the aortic root in Notch1.129S6+/- mice, RNA-sequencing was performed on proximal and distal ascending aortic tissue from Notch1.129S6+/- mice and wildtype littermates at 2 months of age. Transcriptome analysis was utilized to better understand why the dilation was localized to the aortic root. Hierarchical cluster analysis grouped these samples based on location first and then genotype, and showed that cells of the proximal and distal ascending aorta have distinct gene expression patterns in vivo.
Notch1 haploinsufficiency causes ascending aortic aneurysms in mice.
Age, Specimen part, Cell line, Subject
View SamplesWe report an applicaton of small RNA sequencing using high throughput next generation sequencing to identify the small RNA content of cell lines. By sequencing over 30 million reads we could identify a new class of small RNAs previousy observed with tiling arrays and mapping to promoter regions of coding genes. We also identified a large number of small RNAs corresponding to internal exons of coding genes. By using different enzymatic treatments and immunoprecipitation experiments, we have determined that both the promoter associated small RNAs as well as ones within the body of the genes bear 5'' cap structures. Overall design: Examination of the expression of small RNAs (<200nt).
Post-transcriptional processing generates a diversity of 5'-modified long and short RNAs.
No sample metadata fields
View SamplesGM-CSF receptor- deficient (Csf2rb/ or KO) mice develop a lung disease identical to hereditary pulmonary alveolar proteinosis (hPAP) in humans with recessive CSF2RA or CSF2RB mutations that impair GM-CSF receptor function. We performed pulmonary macrophage transplantation (PMT) of bone marrow derived macrophages (BMDMs) without myeloablation in Csf2rb/mice. BMDMs were administered by endotracheal instillation into 2 month-old Csf2rb/ mice. Results demonstrated that PMT therapeutic of hPAP in Csf2rb/ mice was highly efficacious and durable. Alveolar macrophages were isolated by bronchoalveolar lavage one year after administration subjected to microarray analysis to determine the effects of PMT therapy on the global gene expression profile.
Pulmonary macrophage transplantation therapy.
Specimen part, Treatment
View Samples