A Single cell expression atlas of muscle and dermis during regeneration after wounding in Acomys cahirinus - an adult mammal model for de novo muscle regeneration

Acomys cahirinus 受伤后再生过程中肌肉和真皮的单细胞表达图谱 - 一种用于从头肌肉再生的成年哺乳动物模型

• 批准号: 9806424
• 负责人: William B Barbazuk
• 金额: $ 22.44万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9806424
• 关键词: Acomys; Adult; Atlases; B-Lymphocytes; Blood Cells; Cells; Chromium; Cicatrix; Collagen Gene; Community Medicine; Connective Tissue; Data; Dermal; Dermis; Development; Elements; Embryo; Environment; Epithelium; Excision; Extracellular Matrix; Fibroblasts; Fibrosis; Future; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic; Genomics; Goals; Hair; Hair follicle structure; Human; Immune; Immune response; Immune system; Immunohistochemistry; Immunophenotyping; In Situ Hybridization; Individual; Knowledge; Label; Lead; Life; Maintenance; Mammals; Mediating; Medical; Medicine; Methodology; Modeling; Mus; Muscle; Muscle Cells; Muscle Development; Muscle Fibers; Myogenic Regulatory Factors; Myosin ATPase; Natural regeneration; Organ; Organism; Outcome; Pattern; Physiological; Population; Production; Proliferating; Public Domains; Regenerative Medicine; Regulator Genes; Research; Resources; Sebaceous Glands; Signal Transduction; Skeletal Muscle; Skin; Skin wound; Soldier; Structural Genes; Structure; T-Lymphocyte; Testing; Therapeutic; Time; Tissues; Translating; Up-Regulation; Wound Healing; arm; expectation; in vivo; macrophage; muscle regeneration; new therapeutic target; prevent; programs; reference genome; regenerative; repaired; response; response to injury; single-cell RNA sequencing; skin regeneration; stem cell population; therapeutic development; tissue regeneration; transcriptome; transcriptome sequencing; whole genome; wound; wound epidermis

Abstract: It is of major significance that we have discovered that during complete skin regeneration in the spiny mouse, Acomys, the skeletal muscle of the lower layers of the skin are regenerated despite the removal of all the connective tissue components of this tissue. This is in contrast to humans and the lab mouse, Mus, where the skin fibroses with a scar and no muscle is regenerated. The medical importance of this observation for both civilians and soldiers is profound because Acomys can also perfectly regenerate damage through the middle of a muscle belly. We propose here to take our recent microarray, qPCR and RNA-seq analysis of whole skin regeneration to the single cell level with single cell RNA-Seq (scRNA-seq) so that gene regulation patterns of the individual tissue components which make up the regenerating skin can be identified. This project will develop and utilize immunophenotyping panels and comprehensive single cell gene expression assays scRNA-Seq to resolve expression of individual cells and assess changes in tissue cell sub-populations across time between the Mus (scarring) and Acomys (regenerating). The outcome of this project is to identify the gene regulatory networks which characterize individual populations in a regenerating environment in contrast to a scarring environment, and to provide this as a resource to the regenerative medicine community. Future directions will be centered on functionally testing crucial genes for their ability to induce regeneration (hair follicles, sebaceous glands, skeletal muscle) in lieu of scarring with clear implications for its extrapolation to the human condition.

摘要： 具有重大意义的是，我们发现在多刺小鼠的完全皮肤再生过程中， Acomys，皮肤下层的骨骼肌再生，尽管去除了所有的 这种组织的结缔组织成分。这与人类和实验室小鼠Mus形成对比， 皮肤纤维化，有疤痕，没有肌肉再生。这一观察结果的医学重要性， 平民和士兵是深刻的，因为Acomys也可以完美地通过中间再生伤害， 大肚腩我们在这里建议采取我们最近的微阵列，qPCR和RNA-seq分析整个皮肤 用单细胞RNA-Seq（scRNA-seq）将再生的基因表达水平提高到单细胞水平， 可以识别构成再生皮肤的各个组织成分。该项目将 开发和利用免疫分型板和全面的单细胞基因表达测定 scRNA-Seq用于解析单个细胞的表达，并评估组织细胞亚群的变化。 Mus（疤痕）和Acomys（再生）之间的时间。这个项目的结果是确定了 调控网络，其特征在于在再生环境中的个体种群， 疤痕的环境，并提供这作为一种资源，以再生医学界。未来 方向将集中在功能测试关键基因的能力，以诱导再生（头发 毛囊，皮脂腺，骨骼肌）代替瘢痕形成，明确暗示其外推到 人类的状况