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Developing human gonad organoids to promote germ cell differentiation

开发人类性腺类器官以促进生殖细胞分化

基本信息

批准号：
10475265
负责人：
Michael Buszczak
金额：
$ 20.5万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10475265
关键词：
Adopted Affect Animal Model Automobile Driving Back Benchmarking Biological Models Cell Differentiation process Cell Maturation Cell physiology Cells Coculture Techniques Complex DNA Double Strand Break DNA Repair Defect Derivation procedure Development Diagnosis Double Strand Break Repair Down Syndrome Elements Engineering Exhibits Experimental Models Fetal Development Fostering Gametogenesis Genetic Diseases Genome Germ Cells Goals Gonadal structure Human In Vitro Individual Infertility Intermediate Mesoderm Invaded Licensing Mammalian Cell Mammals Medical Meiosis Methods Mus Oogenesis Organoids Ovarian Ovarian aging Ovary Pathway interactions Planets Population Process Property Protocols documentation Rattus Reproduction Reproductive Biology Reproductive Sciences Science Selfish DNA Somatic Cell Standardization Structure of primordial sex cell Study models Supporting Cell Testing Totipotency Work age related cell type design egg evidence base experience experimental study fetal human female human fetal cells in vivo induced pluripotent stem cell induced pluripotent stem cell technology insight kidney cell novel novel therapeutics prevent reconstitution single cell sequencing sperm cell success

项目摘要

Summary Germ cells are essential for the propagation of our species. Disruption of normal germ cell differentiation and function can result in infertility and genetic disorders in the progeny of affected individuals. However, many of the mechanisms that govern the formation and function of germ cells remain poorly understood. Our long-term goal is to identify and characterize pathways that regulate germ cell specific processes. However, the study of human gametogenesis remains largely impractical because specific steps of the process remain experimentally inaccessible. In addition, there are key differences between human germ cells and those of other mammals including mice and rats, limiting the usefulness of animal models for studying and manipulating specific aspects of human gametogenesis. To overcome these obstacles, we propose to engineer a transformative and scalable in vitro platform for reconstituting human gametogenesis. Towards this goal, we seek to develop novel methods for driving human induced pluripotent stem (iPS) cells to differentiate into every cell type found within human female gonads. Based of evidence from experimental models, we anticipate mixing iPS cell-derived germ cells with the appropriate combination of iPS cell-derived somatic support cells will promote further steps in the process of gametogenesis. The successful completion of this proposal will revolutionize the study of human reproduction and provide a scalable platform for developing new therapies to treat infertility and prevent a broad range of genetic disorders.

总结