Understanding Appendage Regeneration in Mice

了解小鼠附肢再生

• 批准号: 8881106
• 负责人: Thomas H. Leung
• 金额: $ 12.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8881106
• 关键词: ATAC-seq; Active Sites; Adult; Aging; Animals; Architecture; Automobile Driving; Award; Binding; Biological Assay; Biology; Blood Vessels; Body part; Cartilage; Cell Aging; Cell Cycle; Cell Cycle Arrest; Cell Lineage; Cells; Chromatin; Clinical; Collaborations; Complement; Cyclin-Dependent Kinase Inhibitor; DNA Repair; Data; Dermatology; Developmental Biology; Ear; Enhancers; Ethics; Exhibits; Fluorescence-Activated Cell Sorting; Future; Gene Expression; Genetic; Genomics; Germ Layers; Hair; Harvest; Healed; Human; Invertebrates; Knockout Mice; Knowledge; Laboratories; Mammals; Maps; Measures; Mediating; Mediator of activation protein; Mentors; Messenger RNA; Modeling; Molecular; Molecular Biology; Multipotent Stem Cells; Mus; Natural regeneration; Organism; Pathway interactions; Physicians; Population; Positioning Attribute; Process; Proteins; Regenerative Medicine; Regulator Genes; Research; Research Personnel; Resources; Role; Salamander; Scientist; Site; Skin; Stem cells; Structure; Techniques; Testing; Time; Tissues; Training; Translating; Transposase; Trauma; Undifferentiated; Universities; Work; appendage; base; blastema; career development; cell behavior; cell type; healing; in vivo; induced pluripotent stem cell; insight; keratinocyte; limb regeneration; mouse model; multipotent cell; progenitor; programs; promoter; public health relevance; research study; response; self-renewal; stem cell biology; tissue regeneration; tool; transcriptome sequencing; wound

7. Project Summary/Abstract One of the great mysteries in biology is how do certain animals regenerate lost body parts in response to trauma. Few examples of tissue regeneration exist in mammals, and studies of tissue regeneration in non- mammalian species are limited by a lack of molecular tools. This research plan aims to elucidate how mammalian tissue regeneration unfolds in a genetically defined mouse model of tissue regeneration. Aim #1 will determine the cellular basis of tissue regeneration utilizing developmental biology, lineage tracing, and conditional mouse genetics. Aim #2 will determine the role of a specific protein in regulating gene expression and chromatin accessibility during tissue regeneration. Aim #2 will utilize quantitative mRNA sequencing (RNA-Seq) and a new technique to footprint chromatin accessibility (ATAC-Seq). Successful completion of the proposed aims will greatly advance our understanding of how mammalian tissue regeneration unfolds, and this knowledge may offer insights on how to trigger tissue regeneration in humans and impact future strategies in regenerative medicine. This award will enable the principle investigator, a dermatology trained physician-scientist, to receive intensive training in skin biology, developmental biology, and genomics, and to develop an independent research program. Additionally, Dr. Leung will complete structured career development including didactic sessions, training in ethical conduct, and training in laboratory management. Stanford University is providing him full institutional support, extensive resources, and opportunity for collaborations with experts in the field. The Stanford Department of Dermatology has a strong track record in mentoring dermatology physician-scientists to independent positions. This award will help Dr. Leung transition to a full-time academic tenure-track position where he will spend 90% of his time on research and 10% on clinical activities.

7.项目总结/摘要 生物学中最大的谜团之一是，某些动物如何再生失去的身体部位， 外伤在哺乳动物中，组织再生的例子很少，在非哺乳动物中的组织再生研究也很少。 哺乳动物物种受到缺乏分子工具的限制。这项研究计划旨在阐明如何 哺乳动物组织再生在遗传上确定的组织再生小鼠模型中展开。目标1 将利用发育生物学，谱系追踪， 条件小鼠遗传学目标#2将确定特定蛋白质在调节基因表达中的作用 和组织再生过程中染色质的可接近性。目标#2将利用定量mRNA测序 （RNA-Seq）和足迹染色质可及性的新技术（ATAC-Seq）。成功完成 提出的目标将大大推进我们对哺乳动物组织再生如何展开的理解， 这些知识可以提供关于如何触发人类组织再生的见解，并影响未来的策略， 再生医学 该奖项将使主要研究者，皮肤科训练有素的医生，科学家，接受密集的 在皮肤生物学，发育生物学和基因组学的培训，并制定一个独立的研究 程序.此外，梁博士将完成结构化的职业发展，包括教学会议， 道德操守培训和实验室管理培训。斯坦福大学将为他提供 机构支持、广泛的资源以及与该领域专家合作的机会。的 斯坦福大学皮肤科系在指导皮肤科医生-科学家方面有着良好的记录 独立的立场。该奖项将帮助梁博士过渡到全职学术终身职位 他将把90%的时间用于研究，10%的时间用于临床活动。