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: 10928630
• 负责人: Stefania Dell'Orso
• 金额: $ 140.85万
• 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/10928630
• 关键词: 3-Dimensional; ATAC-seq; Adult; Age; Animal Model; Autoantibodies; Autoimmune Diseases; B-Cell Activation; Binding; Bone Diseases; CHD4 gene; COVID-19; Cell Lineage; Cell Maintenance; Cells; ChIP-seq; Chromatin; Classification; Clinical; Clinical Research; Complement; Consultations; DNA; DNA methylation profiling; DNA-Protein Interaction; Dermatomyositis; Disease model; Elderly; Enhancers; Epigenetic Process; Gene Expression; Gene Expression Regulation; Genes; Genetic Determinism; Genetic Transcription; Genome; Genomics; Helper-Inducer T-Lymphocyte; Hi-C; Histones; Homeostasis; Human; Immune checkpoint inhibitor; In Vitro; Interferon Type II; Interferons; Maps; Mesoderm; Metabolism; Methylation; Molecular; Mus; Muscle; Muscle Fibers; Muscle satellite cell; Musculoskeletal Diseases; Myelogenous; Myopathy; Myositis; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Natural regeneration; NuRD complex; Nuclear Structure; Nucleosomes; Pathogenesis; Patients; Phenotype; Polycomb; Population; Population Study; Post-Transcriptional Regulation; Proteins; Protocols documentation; RNA; RNA-Binding Proteins; Regulation; Regulator Genes; Reproducibility; Research; Research Personnel; Research Project Grants; Research Support; Resolution; Role; SYK gene; Sampling; Services; Signal Transduction; Skin; Small RNA; Somatic Mutation; Specific qualifier value; Systemic Lupus Erythematosus; T-Lymphocyte; Targeted Resequencing; Technology; Training; Translation Initiation; autoinflammatory diseases; cell fate specification; derepression; epigenomics; exome sequencing; genome-wide; human model; human subject; improved; in vivo; instrument; mRNA sequencing; mouse model; neutrophil; next generation sequencing; notch protein; overexpression; patient population; peripheral blood; progenitor; satellite cell; single cell analysis; single-cell RNA sequencing; skin disorder; stem cells; syntax; transcription factor; transcriptome; transcriptome sequencing; transcriptomics; translational study; whole genome

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.

基因组技术部积极参与了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，揭示细胞命运规范和功能的分子机制。 - 通过 scRNAseq 研究循环人类中性粒细胞的转录子集。中性粒细胞可分为可在健康人类受试者中复制的转录簇。外周血中性粒细胞从相对不成熟 (Nh0) 细胞，通过过渡表型 (Nh1)，转变为由相对转录不活动 (Nh2) 或 I 型 IFN 诱导基因高表达 (Nh3) 定义的两个终点之一。 - 染色质景观和调控小鼠表皮分化的调控网络的研究 -抑制脾酪氨酸激酶在恢复COVID-19骨髓稳态中的作用的研究 - UBA1 体细胞突变和严重成人发病的自身炎症性疾病的研究。 - 使用不同测序技术（ChIP-Seq、mRNA-seq、全基因组甲基-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 细胞细胞激活过程中表观遗传特征变化的动态及其对细胞激活的影响。 - RNA 结合蛋白 (RBP) 对转录后基因调控的影响。 - 选定的 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 ESC 的转录组学、调控语法和增强子鉴定 - 体外和体内生成和分离小鼠肌原祖细胞的方案 - 皮肤细胞谱系的规范和维护，以及皮肤干细胞调节的研究。 - 了解染色质调节因子（例如 Polycomb 蛋白、转录因子 Pst1 和 eRNA）在肌肉分化过程中调节基因表达的活性。 - Ezh1 通过 Notch 信号传导的非规范调节维持小鼠肌肉干细胞静止的作用 - 发现骨骼肌细胞规范、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、表观遗传学和功能分析表明中性粒细胞多样性与系统性红斑狼疮的发病机制有关。 - 肌炎中干扰素-γ诱导的补体局部 RNA 协调过度表达 - 免疫检查点抑制剂引起的肌炎的不同亚型 - 通过 ATAC-seq 分析静态和分化肌肉干细胞（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和分化/细胞命运规范模型中的单细胞转录组分析。 - 皮肌炎和抗 Mi2 自身抗体患者肌肉中 CHD4/NuRD 调节基因的转录去抑制 -FoxO 保持真正的肌肉干细胞静止状态直至老年。

项目成果

JAK Inhibition Differentially Affects NK Cell and ILC1 Homeostasis.

JAK 抑制对 NK 细胞和 ILC1 稳态有不同影响。

• DOI: 10.3389/fimmu.2019.02972
• 发表时间: 2019
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Vian,Laura;Le,MimiT;Gazaniga,Nathalia;Kieltyka,Jacqueline;Liu,Christine;Pietropaolo,Giuseppe;Dell'Orso,Stefania;Brooks,StephenR;Furumoto,Yasuko;Thomas,CraigJ;O'Shea,JohnJ;Sciumè,Giuseppe;Gadina,Massimo
• 通讯作者: Gadina,Massimo

Identification of Unique microRNA Profiles in Different Types of Idiopathic Inflammatory Myopathy.

在不同类型的特发性炎症性肌病中识别独特的microRNA谱。

• DOI: 10.3390/cells12172198
• 发表时间: 2023-09-02
• 期刊: Cells
• 影响因子: 6

Epigenomic Views of Innate Lymphoid Cells.

• DOI: 10.3389/fimmu.2017.01579
• 发表时间: 2017
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Sciumè G;Shih HY;Mikami Y;O'Shea JJ
• 通讯作者: O'Shea JJ

Single-Cell Analysis Reveals the Range of Transcriptional States of Circulating Human Neutrophils.

• DOI: 10.4049/jimmunol.2200154
• 发表时间: 2022-08-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Wigerblad G;Cao Q;Brooks S;Naz F;Gadkari M;Jiang K;Gupta S;O'Neil L;Dell'Orso S;Kaplan MJ;Franco LM
• 通讯作者: Franco LM

Non-classical monocytes as mediators of tissue destruction in arthritis.

• DOI: 10.1136/annrheumdis-2018-213250
• 发表时间: 2018-10
• 期刊: Annals of the rheumatic diseases
• 影响因子: 27.4
• 作者: Puchner A;Saferding V;Bonelli M;Mikami Y;Hofmann M;Brunner JS;Caldera M;Goncalves-Alves E;Binder NB;Fischer A;Simader E;Steiner CW;Leiss H;Hayer S;Niederreiter B;Karonitsch T;Koenders MI;Podesser BK;O'Shea JJ;Menche J;Smolen JS;Redlich K;Blüml S
• 通讯作者: Blüml S