The highly conserved protein eIF5A found in archaea and all eucaryotes uniquely contains the posttranslationally formed amino acid hypusine. Despite being essential the functions of this protein and its modification remain unclear. To gain more insight into these functions temperature sensitive mutants of the human EIF5A1 were characterized in the yeast Saccharomyces cerevisiae.
Temperature-sensitive eIF5A mutant accumulates transcripts targeted to the nonsense-mediated decay pathway.
No sample metadata fields
View SamplesHuman and mouse blood each contain two monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two species subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPAR signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse.
Comparison of gene expression profiles between human and mouse monocyte subsets.
No sample metadata fields
View SamplesHuman and mouse blood each contain two monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two species subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPAR signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse.
Comparison of gene expression profiles between human and mouse monocyte subsets.
No sample metadata fields
View SamplesCNS autoimmunity is induced by autoreactive T cells reactive against CNS antigen. However how these T cells become able to transgress the blood brain barrier is not CNS autoimmunity is induced by autoreactive T cells reactive against CNS antigen. Here a gene expression profile of the pathogenic T cells in different functional states was performed.
T cells become licensed in the lung to enter the central nervous system.
Sex, Specimen part
View SamplesAcute myeloid leukemia (AML) is characterized by molecular heterogeneity. As commonly altered genomic regions point to candidate genes involved in leukemogenesis, we used microarray-based comparative genomic hybridization and single nucleotide polymorphism profiling data of 391 AML cases to further narrow down genomic regions of interest. Targeted-resequencing of 1000 genes located in the critical regions was performed in a representative cohort of 50 AML samples comprising all major cytogenetic subgroups. We identified 120 missense/nonsense mutations as well as 60 insertions/deletions affecting 73 different genes (~3.6 tumor-specific aberrations/AML). While most of the newly identified alterations were non-recurrent, we observed a number of mutations affecting genes involved in epigenetic regulation including known candidates like TET2, TET1, DNMT3A and DNMT1, as well as mutations in the histone methyltransferases NSD1, EZH2 and MLL3. Furthermore, we found mutations in the splicing factor SFPQ and in the non-classical regulators of mRNA-processing CTCF and RAD21. These splicing-related mutations affected 10% of AML patients in a mutually exclusive manner. In conclusion, we could identify a significant enrichment of alterations in genes involved in aberrant splicing and epigenetic regulation in genomic regions commonly altered in AML, highlighting their important role in the molecular pathogenesis of AML.
Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing.
Specimen part, Disease
View SamplesIncreasing the understanding of the impact of changes in oncogenes and tumor suppressor genes is essential for improving the management of lung cancer. Recently, we identified a new mouse lung-specific tumor suppressor - the G-protein coupled receptor 5A (Gprc5a). We sought to understand the molecular consequences of Gprc5a loss and towards this we performed microarray analysis of the transcriptomes of lung epithelial cells cultured from normal tracheas of Gprc5a knockout and wild-type mice to define a loss-of-Gprc5a gene signature. Moreover, we analyzed differential gene expression patterns between Gprc5a knockout normal lung epithelial cells as well as lung adenocarcinoma cells isolated and cultured from tumors of NNK-exposed Gprc5a knockout mice.
A Gprc5a tumor suppressor loss of expression signature is conserved, prevalent, and associated with survival in human lung adenocarcinomas.
Specimen part
View SamplesWe sought to identify the carcinogenic mechanisms involved in RKO cell line with no evidence of activated -catenin/TCF regulated transcription, by comparison its gene expression profile to that of group of colorectal cancer cell lines selected to be mismatch repair
The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription.
Cell line
View SamplesWe have identified the molecular (transcriptional) signatures associated with muscle remodeling in response to rehabilitation in a patient cohort. Subjects with a closed malleolus fracture treated conservatively with 6 weeks of cast immobilization are recruited. Then subjects are enrolled in a 6 weeks structured rehabilitation program focusing on progressive resistance training of the ankle plantar flexor muscles. Phenotypic measurements are performed before (pre-rehab), during (mid-rehab, 3 weeks) and immediately after (post-rehab, 6 weeks) the rehabilitation intervention. The maximal cross-sectional area (muscle size) and peak torque (muscle strength) are quantified using isometric and isokinetic tests in combination with 3D-magnetic resonance imaging. Ankle plantar flexor muscle size and strength measurements are also performed on the uninvolved limb (serves as a control) at 4 months post-immobilization. Measurements are also acquired from the contralateral leg, which serves as an internal control.
Molecular signatures of differential responses to exercise trainings during rehabilitation.
Sex, Time
View SamplesStudies in rodents and newborn humans, demonstrate the influence of brown adipose tissue (BAT) in temperature control and energy balance, which also has a critical role in the regulation of body weight. Here, we obtained samples of epicardial adipose tissue (EAT) from neonates, infants and children in order to compare the changes in gene expression with age
Gene pathway development in human epicardial adipose tissue during early life.
Sex, Specimen part
View SamplesGenes differentially expressed among cells constituting an in vitro human lung carcinogenesis model consisting of normal, immortalized, transformed and tumorigenic bronchial epithelial cells were identified. The differentially expressed genes were then analyzed to determine their relevance to the gene expression patterns of clinical non-small cell lung cancer (NSCLC) samples as well as the clinical outcome of patients with this disease.
Identification of gene signatures and molecular markers for human lung cancer prognosis using an in vitro lung carcinogenesis system.
Cell line
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