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

基因组技术科一直积极参与NIAMS的大量研究项目，其中包括： - 分析T淋巴细胞的基因组结构，以了解T辅助细胞命运规范和功能的基因调控机制。ATAC-Seq、RNA-Seq和ChIP-Seq已用于绘制染色质状态、染色质可及性和转录组图谱，揭示细胞命运指定和功能的分子机制。 - 通过scRNAseq研究循环人中性粒细胞的转录亚群。嗜中性粒细胞可以被分类为在健康人类受试者中可再现的转录簇。外周血中性粒细胞从相对不成熟（Nh 0）的细胞，通过过渡表型（Nh 1），到两个端点之一，定义为相对转录活性（Nh 2）或高表达的I型IFN诱导基因（Nh 3）。 - 小鼠表皮细胞分化的染色质景观及其调控网络的研究 - 研究抑制脾酪氨酸激酶在恢复COVID-19骨髓稳态中的作用 - UBA 1体细胞突变与严重成人发病性自身炎症性疾病的研究 - 通过使用不同测序技术（ChIP-Seq、mRNA-seq、全基因组甲基化-seq、4C、Hi-C）比较组蛋白标记、核小体结合、转录因子结合、DNA（去）甲基化和3-D核结构，在B细胞的细胞活化期间观察到的表观遗传特征变化的动态及其对细胞活化的影响。 - RNA结合蛋白对转录后基因调控的影响。 - 选择RBP对翻译起始和延伸的影响。 - 单细胞分辨率下中胚层诱导的ESCs中的转录组学、调控语法和增强子鉴定 - 体外和体内产生和分离小鼠肌源性祖细胞的方案 - 皮肤细胞谱系的规范和维护，以及皮肤干细胞调节的研究。 - 了解染色质调节剂的活性，如Polycomb蛋白，转录因子Pst 1和eRNA在肌肉分化过程中调节基因表达。 - Ezh 1通过非经典调节Notch信号通路维持小鼠肌肉干细胞静止 - 发现在骨骼肌细胞的特化、分化和再生过程中调节代谢和表观遗传学的分子机制。 - 转录组学、表观遗传学和功能分析提示中性粒细胞多样性参与系统性红斑狼疮的发病机制。 - γ-干扰素诱导的补体协同局部RNA过表达在肌炎中的作用 - 免疫检查点通道诱导的肌炎的不同子集 - 通过ATAC-seq分析静止和分化的肌肉干细胞（卫星细胞）的染色质可及性和基因组组织。 - 在几种人类和小鼠疾病模型和分化/细胞命运规范中的单细胞转录组分析。 - 皮肌炎患者肌肉中CHD 4/NuRD调节基因的转录去抑制和抗Mi2自身抗体 -FoxO保持真正的肌肉干细胞静止状态，直到老年。

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.