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Simultaneous Single-cell Lineage Tracing and Transcriptome Analysis for Mapping Human and Mouse Retinal Development

同时进行单细胞谱系追踪和转录组分析，绘制人类和小鼠视网膜发育图谱

基本信息

批准号：
10400229
负责人：
Claire Bell
金额：
$ 2.04万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2022-09-23
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10400229
关键词：
Animal Model Bioinformatics Biological Models Blindness Cell Differentiation process Cell Lineage Cell Therapy Cells Cessation of life Communication Complex Data Data Set Development Developmental Process Disease Education Fetal Tissues Functional disorder Future Gene Expression Gene Targeting Genes Genetic Goals Graduate Education Human Human Genetics Impairment In Vitro Institution Knowledge Laboratories Lead Maps Mentors Mentorship Methods Modeling Molecular Molecular Profiling Molecular and Cellular Biology Mus Myristica fragrans Neurons Nuclear Organoids Pathway interactions Patients Pharmaceutical Preparations Principal Investigator Process Rattus Research Research Training Resolution Retina Retinal Diseases Stem Cell Development Study models Supporting Cell System Technology Therapeutic Tissue-Specific Gene Expression Training Training Programs Vision research base career cell type genome editing genomic locus graduate student human fetus tissue human stem cells improved in utero in vivo insight medical schools meetings molecular drug target novel novel strategies pre-doctoral prevent responsible research conduct retinal neuron retinal progenitor cell single cell analysis skills spine bone structure stem cell biology stem cells targeted treatment tool transcriptome transcriptome sequencing transcriptomics transdifferentiation

项目摘要

Project Summary/Abstract Retinal development occurs as a common retinal progenitor cell is differentiated into the seven classes of retinal neurons and supporting cells that organize into the three layers of the retina. This developmental process has primarily been studied in mace, as it takes place largely in utero, and the difficulty of obtaining human fetal tissue has put significant limitations on the ability to study the detailed mechanisms of early human retinal development. Understanding the genetic complexity of retinal cell fate decisions and cell lineages holds implications for our understanding of retinal disease. Retinal diseases can cause the dysfunction and death of specific retinal cell types, leading to vision loss and blindness in patients. Many genes associated with retinal diseases have also been implicated in normal retinal development, and knowledge of the correct molecular processes will give context to abnormal processes observed in disease states. Recently, human stem cell- derived retinal organoids have become an established model for studying the cellular and molecular processes of retinal development. The goal of this study is to perform simultaneous RNA sequencing and lineage tracing in vivo in murine retinas and in vitro in developing human retinal organoids at single-cell resolution in order to create detailed maps of human and mouse retina formation. The proposed study will build upon our understanding of mice as a model organism for retinal studies and allow the identification of genes and pathways involved in the precise cell fate decisions that occur during human retinal development. The ultimate comparison of these two model systems may further highlight and prioritize genes of key importance. This knowledge will help to develop and improve therapeutic strategies for treating retinal diseases. This proposal explains a research strategy and training plan to develop the principal investigator, Ms. Claire Wenger, throughout her graduate education. Ms. Wenger has completed her third-year as a graduate student in the Human Genetics Predoctoral Training Program at Johns Hopkins School of Medicine. After graduating, it is her goal to continue to pursue vision research and embark on a career as a principal investigator at a research- based institution. Ms. Wenger’s education must be thorough and interdisciplinary in order to develop her skills in molecular and cellular biology, bioinformatics, responsible conduct of research, scientific communication, and mentorship. Her training plan includes coursework, seminars, meetings, and laboratory skills taught to her by a diverse set of mentors. The proposed research and training strategies will provide Ms. Wenger with the necessary tools to excel in her graduate career and successfully attain her future goals.

项目总结/文摘