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Epigenetic Regulation of Germ Cell Differentiation from a Stem Cell Lineage

干细胞谱系生殖细胞分化的表观遗传调控

基本信息

批准号：
10033955
负责人：
XIN CHEN
金额：
$ 34.3万
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：
2020-07-10 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10033955
关键词：
Address Area Biochemical Biological Biological Models Biology Biophysics Cancer Biology Cell Culture System Cell Cycle Cell Cycle Progression Cell Differentiation process Cell Lineage Cell Maintenance Cell physiology Cells Cellular biology ChIP-seq Chromatin Chromatin Fiber Complex DNA DNA Sequence DNA biosynthesis DNA replication fork Data Diabetes Mellitus Disease Drosophila genus Epigenetic Process Event Fiber Gene Expression Gene Silencing Genes Genetic Genetic Transcription Genomic DNA Genomic Segment Genomics Germ Cells Histones In Vitro Infertility Label Light Malignant Neoplasms Mammals Maps Methods Molecular Molecular Biology Molecular Genetics Movement Muscular Dystrophies Nerve Degeneration Okazaki fragments Phase Play Polycomb Proliferating Cell Nuclear Antigen Proteins RNA Regenerative Medicine Regulation Replication Initiation Replication Origin Reproductive Biology Research Research Personnel Role S Phase Series Somatic Cell Structure System Techniques Testing Therapeutic Work adult stem cell base dimer epigenetic regulation experimental study genomic locus germline stem cells histone modification human disease in vivo male novel origin recognition complex programs public health relevance self-renewal stem cell biology stem cell population stem cell proliferation stem cells stem-like cell tissue degeneration transcriptome transcriptome sequencing

项目摘要

Title: Epigenetic Regulation of Germ Cell Differentiation from a Stem Cell Lineage Project Summary: Many human diseases are caused by imbalances between self-renewal/proliferation versus differentiation of adult stem cells. Therefore, it is critical to characterize the molecular and cellular mechanisms that regulate stem cell function to understand the diseases such as cancers and tissue degeneration. Additionally, to utilize stem cells in therapeutic applications, it is critical to understand the mechanisms that maintain stem cells, regulate proper proliferation of progenitor cells and program cellular differentiation in stem cell lineages. Stem cell-based regenerative medicine also holds promise for diseases such as cancers, neurodegeneration, muscle dystrophy, diabetes, and infertility. A broad definition of epigenetic mechanisms refers to DNA-associated factors that change gene expression without altering the primary DNA sequences. Epigenetic mechanisms play crucial roles in defining stem cell identity and regulating stem cell activity. Among known epigenetic regulators, the Polycomb group (PcG) transcriptional repressive proteins have critical functions in multiple stem cell lineages across different species from Drosophila to mammals. In addition to their well-characterized functions in silencing gene expression, studies from many labs have shown other roles of PcG in areas such as DNA replication and cell cycle progression. My lab uses the Drosophila male germline stem cell (GSC) lineage as a model system to investigate how epigenetic mechanisms regulate stem cell maintenance, proliferation, differentiation, and dedifferentiation. Our previous studies have shed light on epigenetic mechanisms in regulating multiple events in GSC lineage including GSC maintenance and germ cell differentiation. Our recent work reveals under-appreciated functions of DNA replication and potentially new roles of epigenetic regulators such as Polycomb (Pc). We propose to use well-established and newly developed methods in molecular genetics, cell biology, biophysics and genomics to provide an in-depth and systematic understanding of how key epigenetic players regulate stem cells in vivo. Successful completion of the proposed studies will have a broad impact on stem cell biology, germ cell biology, DNA replication, chromatin biology, cancer biology, reproductive biology, and regenerative medicine.

题目：干细胞谱系中生殖细胞分化的表观遗传调控