cultivate-primary-nasal-epithelial-cells-from-children-reprogram-into

Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced Pluripotent Stem Cells

Nasal epithelial cells (NECs) are the part of the airways that respond to air pollutants and are the first cells infected with respiratory viruses. They ...

Cincinnati Children's Hospital

Dendritic cells (DCs) are important mediators of innate and adaptive immune responses, but the gene networks governing their lineage differentiation and maturation are poorly understood. To gain insight into the mechanisms that promote human DC differentiation and contribute to the acquisition of their functional phenotypes, we performed genome-wide base-resolution mapping of 5-methylcytosine in purified monocytes and in monocyte-derived immature and mature DCs.

DNA methylation dynamics during ex vivo differentiation and maturation of human dendritic cells.

Induced pluripotent stem cells (iPSCs) hold tremendous potential, both as a biological tool to uncover the pathophysiology of disease by creating relevant human cell models and as a source of cells for cell-based therapeutic applications. Studying the reprogramming process will also provide significant insight into tissue development.

Dynamic transcriptional and epigenomic reprogramming from pediatric nasal epithelial cells to induced pluripotent stem cells.

There is considerable heterogeneity in asthma treatment response.

Vanin-1 expression and methylation discriminate pediatric asthma corticosteroid treatment response.

Asthma is a complex disorder influenced by genetics and the environment. Recent findings have linked abnormal DNA methylation in T cells with asthma; however, the potential dysregulation of methylation in airway epithelial cells is unknown. Studies of mouse models of asthma have observed greater levels of 5-hydroxymethylcytosine (5-hmC) and ten-eleven translocation 1 (TET1) expression in lungs. TET proteins are known to catalyze methylation through modification of 5-methylcytosine to 5-hmC.

Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution.

The efficacy of protease inhibitor drugs in hepatitis C virus (HCV) treatment is limited by the selection and expansion of drug-resistant mutations. HCV replication is error-prone and genetic variability within the dominant epitopes ensures its persistence. The aims of this study are to evaluate the role of cellular immune response in the emergence of HCV protease resistance mutations and its effects on treatment outcome. Ten chronically HCV-infected subjects were treated with boceprevir (BOC)-based triple therapy. HCV-RNA was tested for BOC resistance-associated viral variants. HCV protease resistance mutations were investigated pretreatment and 24 weeks post-treatment. Synthetic peptides representing the wild-type and the potential nonstructural (NS)3 variants were used to evaluate T-cell responses and human leukocyte antigen binding. Sustained viral response was achieved in 70% of patients, two patients were treatment nonresponders (NRs) and one was classified as a relapse. Pretreatment, the proportion of drug-resistant variants within individuals was higher in sustained viral responders (SVRs) than in NR patients. However, resistance-associated variants increased in NRs after BOC combined triple therapy. In contrast to NR patients, significant stronger cell-mediated immune responses were observed at the baseline among those who achieved sustained viral response for all T-cell epitopes tested. Despite the increase in cell-mediated immune responses at week 24 in NRs, they failed to control the virus replication, leading to development of overt drug-resistant variants. Our data suggest that strong NS3-specific T-cell immune responses at the baseline may predict a positive outcome of directly acting antiviral-based therapy, and the presence of pre-existent resistance mutations does not play a significant role in the outcome of anti-HCV combined therapy.

Article	Year
DNA methylation dynamics during ex vivo differentiation and maturation of human dendritic cells. Epigenetics & chromatin\| PubMed ID: 25161698	2014
Dynamic transcriptional and epigenomic reprogramming from pediatric nasal epithelial cells to induced pluripotent stem cells. The Journal of allergy and clinical immunology\| PubMed ID: 25441642	2015
Vanin-1 expression and methylation discriminate pediatric asthma corticosteroid treatment response. The Journal of allergy and clinical immunology\| PubMed ID: 25910714	2015
Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution. The Journal of allergy and clinical immunology\| PubMed ID: 26684294	2016
Evaluating the Role of Cellular Immune Responses in the Emergence of HCV NS3 Resistance Mutations During Protease Inhibitor Therapy. Viral immunology\| PubMed ID: 26885675	2016

Ashley Ulm

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