The High Throughput Sequencing Unit has been actively involved in a large number of NIAMS research projects, including: -Analysis of 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 mechanism for cell fate specification and function. - Study of specific regions of the bone sialoprotein (BSP) to determine specific regions of the BSP molecule responsible for promoting tooth root formation, through interacting with integrins, and regulating mineral formation during cementogenesis. - Identification of novel pathophysiologic pathways involved in myositis by comparing the transcriptomes of muscle biopsies from myositis patients with defined myositis autoantibodies. - Mapping of genome-wide double strand breaks using a new technique called END-seq, developed in Dr. Andre A. Nussenzweigs laboratory. - Dynamic of changes 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). - Understanding the activity of chromatin regulators such as Polycomb proteins, the transcription factor Notch, Ago2 and eRNAs in regulating gene expression during muscle differentiation. - Discovering the molecular mechanisms regulating metabolism and epigenetics during specification, differentiation, and regeneration of skeletal muscle cells. -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.
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