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: 10496410
• 负责人: Massimo Gadina
• 金额: $ 139.27万
• 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/10496410
• 关键词: 3-Dimensional; ATAC-seq; Acute; Adult; Age; Animal Model; Atopic Dermatitis; Autoimmune; Autoimmune Diseases; B-Cell Activation; Binding; Biology; Bone Diseases; Cell Differentiation process; Cell Lineage; Cell Maintenance; Cells; Cementogenesis; ChIP-seq; Chromatin; Clinical; Clinical Research; Consultations; DNA; DNA methylation profiling; Disease; Disease model; Eczematous Skin Diseases; Elderly; Endogenous Retroviruses; Enhancers; Epigenetic Process; Equilibrium; Feedback; Gene Expression; Gene Expression Regulation; Genetic Determinism; Genome; Genomics; Helper-Inducer T-Lymphocyte; Hi-C; Histones; Inflammation; Inflammatory; Integrins; Interferon Type I; Intestines; Leukocytes; Libraries; Llama; Lymphoid Cell; Maps; Metabolism; Methylation; MicroRNAs; Minerals; Molecular; Mus; Muscle; Muscle Fibers; Muscle satellite cell; Musculoskeletal Diseases; Myopathy; NK Cell Activation; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Natural regeneration; Nuclear Structure; Nucleosomes; Pathogenesis; Pathway interactions; Polycomb; Population; Population Study; Post-Transcriptional Regulation; Preparation; Protein Binding Domain; Proteins; Protocols documentation; RNA Binding; RNA-Binding Proteins; Regulation; Regulator Genes; Research; Research Personnel; Research Project Grants; Research Support; SARS-CoV-2 variant; Sampling; Scanning; Sebaceous Glands; Services; Sex Differences; Skin; Small RNA; Somatic Mutation; Systemic Lupus Erythematosus; T-Lymphocyte; Targeted Resequencing; Technology; Tooth root structure; Training; Translation Initiation; autoinflammatory; bone sialoprotein; cDNA Library; cell fate specification; cohesin; commensal bacteria; embryonic stem cell; epigenomics; exome sequencing; gene induction; genome-wide; human model; improved; instrument; interleukin-23; mRNA sequencing; mouse model; nanobodies; neutrophil; next generation sequencing; patient population; response; satellite cell; single cell analysis; single-cell RNA sequencing; skin disorder; skin microbiome; skin microbiota; stem cell population; stem cells; transcription factor; transcriptome; transcriptome sequencing; transcriptomics; translational study; tumor; 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. - Study of somatic mutations in UBA1 and severe adult-onset Autoinflammarory Disease - 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 occurs between the skin, the microbiota and resident leukocytes during steady-state and inflammation. - 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, 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. - Transcriptomic, epigenetic, and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus. - 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. -Understanding the roll of cutaneous microbiome in eczematous skin diseases, including atopic dermatitis. -Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism. -MicroRNA-221 and -222 modulate intestinal inflammatory Th17 cell response as negative feedback regulators downstream of interleukin-23. -Rapid Enhancer Remodeling and Transcription Factor Repurposing Enable High Magnitude Gene Induction upon Acute Activation of NK Cells. -Protocol for RNA-seq library preparation starting from a rare muscle stem cell population or a limited number of mouse embryonic stem cells. -FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age. -CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning. -Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants -A non-radioactive, improved PAR-CLIP and small RNA cDNA library preparation protocol. -Posttranscriptional regulation of human endogenous retroviruses by RNA-binding motif protein 4, RBM4 -Loss of DLX3 tumor suppressive function promotes progression of SCC through EGFRERBB2 pathway

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。 - UBA 1基因体细胞突变与成人型严重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，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。 - 在稳态和炎症期间，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，以及皮肤干细胞调节的研究。 - 了解染色质调节因子（例如Polycomb蛋白、转录因子Pst 1、Ago 2和eRNA）在肌肉分化期间调节基因表达的活性。 - 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。 - 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。 - 在几种人类和小鼠疾病模型和分化/细胞命运特化中的单细胞转录组分析。 - 了解皮肤微生物组在湿疹性皮肤病中的作用，包括特应性皮炎。 中性粒细胞生物学的性别差异调节对I型干扰素和免疫代谢的反应。 -MicroRNA-221和-222作为白细胞介素-23下游的负反馈调节剂调节肠道炎性Th 17细胞应答。 - 快速增强子重塑和转录因子重定位使得在NK细胞急性活化时能够进行高幅度的基因诱导。 - 用于从稀有肌肉干细胞群体或有限数量的小鼠胚胎干细胞开始的RNA-seq文库制备的方案。 -FoxO保持真正的肌肉干细胞静止状态，直到老年。 -CTCF协调长距离粘附素驱动的V（D）J重组扫描。 - 来自骆驼科小鼠和美洲驼的纳米抗体中和SARS-CoV-2变体 - 非放射性的、改进的PAR-CLIP和小RNA cDNA文库制备方案。 - 通过RNA结合基序蛋白4（RBM 4）对人内源性逆转录病毒的转录后调节 - DLX 3肿瘤抑制功能的丧失通过EGFRERBB 2途径促进SCC的进展