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

高通量下一代测序：支持肌肉、皮肤、骨骼和自身免疫性疾病的基因组学和表观基因组学研究。

• 批准号: 10023087
• 负责人: Massimo Gadina
• 金额: $ 151.73万
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10023087
• 关键词: 3-Dimensional; ATAC-seq; Animal Model; Autoantibodies; Autoimmune Diseases; Autoimmune Process; B-Cell Activation; Basic Science; Binding; Biopsy; Bone Diseases; Cell Differentiation process; Cell Lineage; Cell Maintenance; Cells; Cementogenesis; ChIP-seq; Chromatin; Clinical; Clinical Research; DNA; Disease model; Epigenetic Process; Equilibrium; Gene Expression; Gene Expression Regulation; Genetic Determinism; Genome; Genomics; Helper-Inducer T-Lymphocyte; Histones; Inflammation; Integrins; Interferons; Leukocytes; Lymphoid Cell; Maps; Metabolism; Methylation; Minerals; Molecular; Muscle; Muscle Fibers; Muscle satellite cell; Musculoskeletal Diseases; Myopathy; Myositis; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Natural regeneration; Nuclear Structure; Nucleosomes; Pathway interactions; Patients; Polycomb; Population; Population Study; Proteins; RNA-Binding Proteins; Regulation; Regulator Genes; Research; Research Project Grants; Sampling; Sebaceous Glands; Skin; Small RNA; Stem cells; T-Lymphocyte; Targeted Resequencing; Technology; Tooth root structure; Translation Initiation; Translational Research; autoinflammatory; bone sialoprotein; cell fate specification; commensal bacteria; epigenomics; genome sequencing; genome-wide; human model; improved; instrument; mRNA sequencing; mouse model; next generation sequencing; novel; patient population; satellite cell; single cell analysis; single-cell RNA sequencing; skin disorder; skin microbiota; transcription factor; transcriptome; transcriptome sequencing; whole genome

The Genome Technology 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. - 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). - impact of RNA binding proteins (RBPs) on posttranscriptional gene regulation (PTGR) - Impact of select RBPs on translation initiation and elongation. - Mutual crosstalk that occur between the skin, the microbiota and resident leukocytes during steady-state and inflammation - Specification and maintenance of cell lineages in the skin, study of the regulation of stem cells in the skin. - Understanding the activity of chromatin regulators such as Polycomb proteins, the transcription factor Pst1, 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. - The Transcription Factor T-bet Limits Amplification of Type I IFN Transcriptome and Circuitry in T Helper 1 Cells. - Homeostatic Control of Sebaceous Glands by Innate Lymphoid Cells Regulates Commensal Bacteria Equilibrium. -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

基因组技术股一直积极参与NIAMS的大量研究项目，包括： - 分析T淋巴细胞的基因组组织，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。 - 研究骨唾液酸蛋白（BSP）的特定区域，以确定BSP分子的特定区域，通过与整合素相互作用促进牙根形成，并在牙骨质形成过程中调节矿物质形成。 - 通过比较肌炎患者肌肉活检的转录组与定义的肌炎自身抗体来识别与肌炎相关的新型病理生理途径。 - 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，观察B细胞活化期间观察到的表观遗传特征的动态变化及其对细胞活化的影响。 - RNA结合蛋白（RBP）对转录后基因调控（PTGR）的影响 - 选择RBP对翻译起始和延伸的影响。 - 稳态和炎症期间皮肤、微生物群和驻留白细胞之间发生的相互串扰 - 皮肤细胞谱系的规范和维护，研究皮肤干细胞的调节。 - 了解染色质调节剂的活性，如Polycomb蛋白，转录因子Pst 1，Ago 2和eRNA在肌肉分化过程中调节基因表达。 - 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。 - 转录因子T-bet限制T辅助细胞1中I型IFN转录组和电路的扩增。 - 皮脂腺内分泌调控调节共生菌群平衡。 - 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。 - 几种人类和小鼠疾病模型中的单细胞转录组分析和分化/细胞命运特化