Molecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia and might contribute to its pathogenesis, we determined global gene expression profiles in muscles of rats aged 6, 12, 18, 21, 24, and 27 months. These rats exhibit sarcopenia beginning at 21 months. Correlation of the gene expression versus muscle mass or age changes, and functional annotation analysis identified gene signatures of sarcopenia distinct from gene signatures of aging. Specifically, mitochondrial energy metabolism (e.g., tricarboxylic acid cycle and oxidative phosphorylation) pathway genes were the most downregulated and most significantly correlated with sarcopenia. Also, perturbed were genes/pathways associated with neuromuscular junction patency (providing molecular evidence of sarcopenia-related functional denervation and neuromuscular junction remodeling), protein degradation, and inflammation. Proteomic analysis of samples at 6, 18, and 27 months confirmed the depletion of mitochondrial energy metabolism proteins and neuromuscular junction proteins. Together, these findings suggest that therapeutic approaches that simultaneously stimulate mitochondrogenesis and reduce muscle proteolysis and inflammation have potential for treating sarcopenia.
Genomic and proteomic profiling reveals reduced mitochondrial function and disruption of the neuromuscular junction driving rat sarcopenia.
Sex, Age, Specimen part
View SamplesAnalysis of gene expression levels from oral tumor and normal tissue. The purpose of this experiment was to compare profiles of gene expression between tumor and negative margin tissue from matched patient samples.
Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations.
Specimen part
View SamplesThe molecular mechanisms underlying the development of bone metastases in breast cancer remain unclear. Disseminated tumour cells (DTCs) in the bone marrow of breast cancer patients are commonly identified, even in early stage disease, but their potential to initiate metastases is not known. The mechanism whereby DTCs become overt metastatic tumour cells (MTCs) is therefore, an area of considerable interest. This study explored the analysable yield of genetic material from human biopsy samples in order to describe differences in gene expression between DTCs and bone MTCs. Thirteen breast cancer patients with bone metastases underwent a CT-guided bone metastasis biopsy and a bone marrow biopsy. Tumour cells were enriched and gene expression profiling was conducted to identify differentially expressed genes. The analysable yield of sufficient RNA for microarray analysis was 60% from bone metastasis biopsies and 80% from bone marrow biopsies. A signature of 133 candidate genes differentially expressed between DTCs and MTCs was identified. Several genes relevant to breast cancer metastasis to bone (osteopontin, CTGF, parathyroid hormone receptor, EGFR) were significantly overexpressed in MTCs as compared to DTCs. Biopsies of bone metastases and bone marrow rarely yield enough tissue for robust molecular biology studies using clinical samples. The findings obtained however are interesting and seem to overlap with the bone metastasis gene expression signature described in murine xenograft models. Larger biopsy specimens or improved RNA extraction techniques may improve analysable yield and feasibility of these techniques.
Mechanisms and pathways of bone metastasis: challenges and pitfalls of performing molecular research on patient samples.
Specimen part, Disease
View SamplesWhile infection of chickens with highly pathogenic avian influenza (HPAI) H5N1 subtypes often leads to complete mortality within 24 to 48 h, infection of ducks in contrast causes mild or no clinical signs. Rapid onsets of fatal disease in chickens, but with no evidence of severe clinical symptoms in ducks, suggest underlying differences in their innate immune mechanisms. To understand the molecular basis for such difference, chicken and duck primary lung cells, infected with a low-pathogenicity avian influenza (LPAI) and two HPAI H5N1 viruses, were subjected to RNA expression profiling using Affymetrix Chicken GeneChip arrays.
Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses.
Age, Specimen part, Treatment
View SamplesRNA from vastus lateralis of healthy young (21-31 year old) and older (62-77 year old) men. Signal data normalized to mean intensity of 500 over all probes sets. Analysis done with Affymetrix Microarray Suite 5.0 software.
Computational method for reducing variance with Affymetrix microarrays.
No sample metadata fields
View SamplesWe present a microarray analysis of primary mouse astrocytes exposed to HIV-1 in culture. Results are compared with previous genomic studies of HIV-1 effect in human astrocytes and human and macaque brains.
Gene expression profiles of HIV-1-infected glia and brain: toward better understanding of the role of astrocytes in HIV-1-associated neurocognitive disorders.
Specimen part, Treatment
View SamplesRNA seq analysis was conducted to determine gene expression in the day 14 ovine conceptus. This was used in conjunction with the day 14 PPARG ChIP-seq analysis to identify genes bound by PPARG which were also expressed or not expressed in the day 14 conceptus. Understanding changes in gene expression during early pregnancy is critical to improving fertility and reproductive efficiency in ruminants. Overall design: RNA seq analysis of 4 conceptuses from 4 individual Day 14 pregnant columbia/rambouillet crossbred ewes
Biological Roles of Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11B1), HSD11B2, and Glucocorticoid Receptor (NR3C1) in Sheep Conceptus Elongation.
Subject
View SamplesRNA seq analysis of laser capture microdissected luminal and glandular epithelium from ewes on day of pregnancy 10, 12, 14, 16 and 20. As well as RNA seq of whole conceptuses, and trophectoderm tissue from day 12, 14, 16 and 20 of pregnancy. Determination of gene expression changes in the uterine epithelium and conceptus during early pregnancy helps to improve our understanding of early pregnancy events and provides a basis of new strategies to improve fertility and reproductive efficiency in ruminants. Overall design: RNA seq analysis of 4 samples of each tissue type (luminal epithelium (LE), glandular epithelium (GE) and conceptus) for 4 animals. Pre-sequencing amplification of LE, GE and day 12 conceptus samples.
Analysis of the Uterine Epithelial and Conceptus Transcriptome and Luminal Fluid Proteome During the Peri-Implantation Period of Pregnancy in Sheep.
Specimen part, Subject
View SamplesBy transcriptome (RNA-Seq) analysis of PC-3 or DU145 prostate cancer cell lines over- or under-expressing NUSAP1, we determined genes that become differentially expressed upon expression changes of NUSAP1. Ingenuity Pathway Analysis revealed that the differentially expressed genes correlated with increased tumor progression and are involved in functions that include cancer, cellular movement, and cell morphology Overall design: Lentiviral infections were used to over- or under-express NUSAP1 or controls in triplicate in PC-3 or DU145 cell lines. Seventy-two or ninety-six hours after infection, total RNA was extracted and purified. The sequencing libraries were prepared with the TruSeq RNA Sample Preparation Kit v2 (Illumina) or TruSeq Stranded mRNA Sample Preparation Kit (Illumina) as directed by the manufacturer’s protocol. Pooled libraries were run on a Hiseq 2000 Sequencing System (Illumina) with 101 base pair single-end reads.
NUSAP1 promotes invasion and metastasis of prostate cancer.
Specimen part, Subject
View SamplesAnalysis of estrogen receptor (ER)-positive MCF7 cell total RNA expression and polysome-assiciated RNA expression following treatment with estradiol (E2) and vehicle (etoh).
Estrogen coordinates translation and transcription, revealing a role for NRSF in human breast cancer cells.
Cell line
View Samples