High Throughput Next Generation Sequencing: supports genomics and epigenomics research in muscle, skin, bone and autoimmune diseases

National Institute Of Arthritis And Musculoskeletal And Skin Diseases

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Abstract

The Genome Technology Section has been actively involved in a large number of NIAMS research projects, including the following: -Analysis of the genomic organization of T lymphocytes to understand gene regulatory mechanisms for T helper cell fate specification and function. ATAC-seq, RNA-Seq, and ChIP-Seq have been used to draw maps of chromatin states, chromatin accessibility, and transcriptome revealing molecular mechanisms for cell fate specification and function. - Study of transcriptional subsets of circulating human neutrophils by scRNAseq. Neutrophils can be classified into transcriptional clusters that are reproducible among healthy human subjects. Peripheral blood neutrophils shift from relatively immature (Nh0) cells, through a transitional phenotype (Nh1), into one of two endpoints defined by either relative transcriptional inactivity (Nh2) or high expression of type I IFN-inducible genes (Nh3). - Study of chromatin landscape and regulatory networks governing murine epidermal differentiation -Study on the role of Spleen tyrosine kinase inhibition to restore myeloid homeostasis in COVID-19 - Study of somatic mutations in UBA1 and severe adult-onset Autoinflammatory Disease. - Dynamics of change in the epigenetic features observed during cellular activation of B-cells and its impacts on cellular activation by comparison of histone marks, nucleosome binding, transcription factor binding, DNA (de)methylation, and 3-D nuclear structure using different sequencing technologies (ChIP-Seq, mRNA-seq, whole genome methyl-seq, 4C, Hi-C). - Impact of RNA binding proteins (RBPs) on posttranscriptional gene regulation. - Impact of select RBPs on translation initiation and elongation. - Transcriptomics, regulatory syntax, and enhancer identification in mesoderm-induced ESCs at single-cell resolution - Protocols to generate and isolate mouse myogenic progenitors both in vitro and in vivo - Specification and maintenance of cell lineages in the skin, and study of the regulation of stem cells in the skin. - Understanding the activity of chromatin regulators such as Polycomb proteins, the transcription factor Pst1, and eRNAs in regulating gene expression during muscle differentiation. - Role of Ezh1 in maintaining murine muscle stem cell quiescence through non-canonical regulation of Notch signaling - Discovering the molecular mechanisms regulating metabolism and epigenetics during specification, differentiation, and regeneration of skeletal muscle cells. - Transcriptomic, epigenetic, and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus. - Coordinated local RNA overexpression of complement induced by interferon-gamma in myositis - Distinct subsets of immune checkpoint inhibitor-induced myositis - Analysis of chromatin accessibility and genomic organization of quiescent and differentiating muscle stem cells (satellite cells) by ATAC-seq. - Analysis of single-cell transcriptome in several human and mouse models of disease and differentiation/cell fate specification. - Transcriptional derepression of CHD4/NuRD-regulated genes in the muscle of patients with dermatomyositis and anti-Mi2 autoantibodies -FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age.