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
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
批准号:
9806424
负责人:
William B Barbazuk
金额:
$22.44万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-08-01 至 2021-07-31
关键词:
AcomysAdultAtlasesB-LymphocytesBlood CellsCellsChromiumCicatrixCollagen GeneCommunity MedicineConnective TissueDataDermalDermisDevelopmentElementsEmbryoEnvironmentEpitheliumExcisionExtracellular MatrixFibroblastsFibrosisFutureGene ExpressionGene Expression ProfilingGene Expression RegulationGenesGeneticGenomicsGoalsHairHair follicle structureHumanImmuneImmune responseImmune systemImmunohistochemistryImmunophenotypingIn Situ HybridizationIndividualKnowledgeLabelLeadLifeMaintenanceMammalsMediatingMedicalMedicineMethodologyModelingMusMuscleMuscle CellsMuscle DevelopmentMuscle FibersMyogenic Regulatory FactorsMyosin ATPaseNatural regenerationOrganOrganismOutcomePatternPhysiologicalPopulationProductionProliferatingPublic DomainsRegenerative MedicineRegulator GenesResearchResourcesSebaceous GlandsSignal TransductionSkeletal MuscleSkinSkin woundSoldierStructural GenesStructureT-LymphocyteTestingTherapeuticTimeTissuesTranslatingUp-RegulationWound Healingarmexpectationin vivomacrophagemuscle regenerationnew therapeutic targetpreventprogramsreference genomeregenerativerepairedresponseresponse to injurysingle-cell RNA sequencingskin regenerationstem cell populationtherapeutic developmenttissue regenerationtranscriptometranscriptome sequencingwhole genomewoundwound epidermis
中文摘要
摘要:
重要的是,我们发现在多刺小鼠的皮肤完全再生过程中,
Acomys,皮肤下层的骨骼肌在去除了所有的
结缔组织这种组织的结缔组织成分。这与人类和实验室小鼠Mus形成了鲜明对比,在那里
有疤痕、没有肌肉的皮肤纤维组织可以再生。这一观察对两人的医学意义
平民和士兵是深刻的,因为Acomys也可以完美地在
肌肉发达的肚子。我们建议将我们最新的微阵列、qpr和rna-seq分析用于整个皮肤。
用单细胞RNA-Seq(scRNA-seq)再生到单细胞水平,从而使基因调控模式
可以识别构成再生皮肤的各个组织成分。这个项目将
开发和利用免疫表型面板和综合单细胞基因表达分析
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(伤疤形成)和Acomys(再生)之间的时间。这个项目的结果是确定了基因
在再生环境中描述个体种群特征的监管网络,与
为再生医学界提供一种资源,以保护再生环境。未来
方向将集中在从功能上测试关键基因诱导再生的能力(头发
毛囊、皮脂腺、骨骼肌),而不是疤痕形成,这显然意味着它的外推到
人类的状况。
英文摘要
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.
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