The goal of this study was to determine the differential expression of specific genes within the papilloma tissues themselves and to characterize the array of host genes that might be important in the pathophysiology of recurrent respiratory papillomatosis.
Immune dysregulation and tumor-associated gene changes in recurrent respiratory papillomatosis: a paired microarray analysis.
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View SamplesRecent research has highlighted that the polyphenols Quercetin (Q) and Tannic acid (TA) are capable of extending the lifespan of C. elegans. To gain a deep understanding of the underlying molecular genetics, we analyzed the global transcriptional patterns of nematodes exposed to Quercetin or Tannic acid concentrations that are non-effective (in lifespan extension), lifespan extending or toxic.
Meta-Analysis of Global Transcriptomics Suggests that Conserved Genetic Pathways are Responsible for Quercetin and Tannic Acid Mediated Longevity in C. elegans.
Specimen part, Treatment
View SamplesAlthough not an affected cell type, skin fibroblasts from individuals with CC-ALD, an early onset X-linked neurological disorder, show defects in very long chain fatty acid (VLCFA) metabolism that provide the basis for clinical diagnostic tests. Skin fibroblasts from CC-ALD patients can be reprogrammed into iPS cells with all the hallmark properties of pluripotency. The iPS cell phenotypes may reflect the tissue-specificity of the lipid metabolic defects found in CC-ALD patients.
The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis.
Specimen part
View SamplesAlthough not an affected cell type, skin fibroblasts from individuals with childhood cerebral adrenoleukodystrophy (CCALD), an early onset X-linked neurological disorder, show defects in very long chain fatty acid (VLCFA) metabolism that provide the basis for clinical diagnostic tests.
The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis.
Specimen part
View SamplesMucispirillum schaedleri is an abundant inhabitant of the intestinal mucus layer of rodents and other animals. To gain insights into its lifestyle, we analyzed the genome and transcriptome of M. schaedleri ASF 457 and tested for traits predicted by the genome using physiological experiments. Although thought to be a mucus degrader, its genome surprisingly predicts that M. schaedleri has limited capacity for degrading host-derived mucosal glycans or other complex polysaccharides. Rather, it may utilize small compounds such as peptides, amino acids, glycerol, and short chain fatty acids. Additionally, it can reduce nitrate and has systems for scavenging oxygen and reactive oxygen species, which accounts for its presence close to the mucosal tissue and during inflammation. Also of note, M. schaedleri harbors a type VI secretion system (T6SS) and several putative effector proteins containing eukaryotic domains, which suggest intimate interactions with the host and a role in inflammation. Examination of the individual phylogenies of all genes in the M. schaedleri genome revealed extensive horizontal gene transfer, primarily from intestinal Epsilon- and Deltaproteobacteria. Though M. schaedleri utilizes non-horizontally-transferred pathways (e.g. nitrate reduction), horizontally-acquired pathways from gut organisms (e.g. T6SS and glycerol-P utilization) are also likely also important for its survival in the intestine, suggesting that lateral gene transfer may have played a key role in facilitating its establishment in the gut ecosystem.
Lifestyle and Horizontal Gene Transfer-Mediated Evolution of <i>Mucispirillum schaedleri</i>, a Core Member of the Murine Gut Microbiota.
Sex, Specimen part, Treatment
View SamplesMultipotent and pluripotent stem cells have significant potential as sources for cell replacement therapies. However, the low yield and quality of in vitro differentiated cells produced from various stem cell sources presents a significant limitation for therapeutic applications. The most mature use of these stem cell products is in the field of transfusion medicine, where stem cell-derived red blood cells (RBCs) have clinically-proven potential as alternative transfusion products. To improve upon current approaches for RBC production, we used insight from both common and rare human genetic variation of blood counts to focus on the SH2B3 gene. By producing loss of function of SH2B3 using targeted knockdown and genome editing approaches in human hematopoietic stem and progenitor cells, as well as human pluripotent stem cells, we are able to significantly improve both the quality and yield of in vitro derived RBCs. We illustrate how insight from human genetic variation can assist in the development of broadly applicable approaches that have tremendous value for regenerative medicine.
Targeted Application of Human Genetic Variation Can Improve Red Blood Cell Production from Stem Cells.
Specimen part
View SamplesLow concentrations of the dissolved leonardite humic acid HuminFeed (HF) prolonged the lifespan and enhanced the thermal stress resistance of the model organism Caenorhabditis elegans. Furthermore growth was impaired and reproduction delayed, effects which have also been identified in other polyphenolic monomers, including tannic acid, rosmarinic acid, and caffeic acid. Moreover, a chemical modification of HF (HF-HQ), which increases its phenolic/quinonoid moieties, magnified the biological impact on C. elegans. To gain a deep insight into the molecular basis of these effects, we performed global transcriptomics on young adult (3 d) and old adult (11 d) nematodes exposed to two concentrations of HF and young adults (3 d) exposed to two concentrations of HF-HQ.
The Nematode Caenorhabditis elegans, Stress and Aging: Identifying the Complex Interplay of Genetic Pathways Following the Treatment with Humic Substances.
Specimen part, Treatment
View SamplesJC virus (JCV) is a ubiquitous human polyomavirus that causes the demyelinating disease Progressive Multifocal Leukoencephalopathy (PML). JCV replicates in limited cell types in culture, predominantly in human glial cells. Thus, productive JCV infection is an indicator of the host cell transcription environment. Following introduction of a replication defective SV40 mutant that expressed large T protein into a heterogeneous culture of human fetal brain cells, multiple phenotypes became immortalized (SVG cells). A subset of SVG cells could support JCV replication. This mixed culture was called SVG cells. In the current study, clonal cell lines were selected from the original SVG cell culture. The SVG-5F4 clone showed low levels of viral growth. The SVG-10B1 clone was highly permissive for JCV DNA replication and gene expression. Microarray analysis revealed that viral infection did not significantly change gene expression in these cells. More resistant 5F4 cells expressed high levels of transcription factors known to inhibit JCV transcription. Interestingly, 5F4 cells highly expressed RNA of markers of Bergman or radial glia and 10B1 cells had high expression of markers of immature glial cells and activation of transcription regulators important for stem/progenitor cell self-renewal. These SVG-derived clonal cell lines provide a biologically relevant model to investigate cell type differences in JCV host range and pathogenesis, as well as neural development.
Clonal immortalized human glial cell lines support varying levels of JC virus infection due to differences in cellular gene expression.
Specimen part, Time
View SamplesLangerhans cell histiocytosis (LCH) is a disease characterized by the accumulation of eponymous CD1a+ Langerin+ Langerhans-cell (LC)-like dendritic cells (DC) of largely unknown origin. Here we have performed comparative transcriptome analysis of highly purified CD207+/CD1a+ Langerhans cell histiocytosis (LCH) cells derived from different locations and disease courses and three major human dendritic cell lineages: epidermal Langerhans cells, myeloid dendritic cells (mDC1) and plasmacytoid dendritic cells (pDC) in order to investigate the relationship between LCH cells and naturally occurring dendritic cells. Data obtained indicate that LCH cells form a distinct DC entity. Furthermore, we have identified transcripts that are uniquely expressed by LCH cells in comparison to LC, mDC1, and pDC, and induce LCH-specific features in human DC.
Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities.
Specimen part
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