Regulation of meiosis in mice

小鼠减数分裂的调节

• 批准号: 9918419
• 负责人: Peijing Jeremy Wang
• 金额: $ 55.96万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-05 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9918419
• 关键词: Animal Model; Biochemical; Biological; Cell Culture System; Cell Culture Techniques; Cells; Chromatin; Chromosome Pairing; Chromosome Segregation; Chromosomes; Complex; Congenital Abnormality; Derivation procedure; Development; Distant; Etiology; Genetic; Genetic Recombination; Genomics; Germ Cells; Goals; Human; In Vitro; Infertility; Lead; Male Infertility; Mammalian Cell; Meiosis; Meiotic Recombination; Molecular; Molecular Abnormality; Monitor; Monosomy; Mus; Organism; Pregnancy loss; Process; Property; Proteins; Proteomics; Regenerative Medicine; Regulation; Reporter; Research; Role; Structure; System; Trisomy; base; cost; cost effective; infertility treatment; innovation; insight; novel; public health relevance; segregation; therapy development

 DESCRIPTION (provided by applicant): The long-term goal of the current application is to elucidate novel molecular networks underlying mammalian meiosis and develop a mammalian cell culture system for in vitro meiosis. Meiosis, a process unique to germ cells, involves pairing synapsis, recombination, desynapsis, and segregation of homologous chromosomes. Genetic abnormalities resulting from meiosis are a leading cause of birth defects, pregnancy loss, and infertility in humans. The structural and functional properties of meiotic chromatin, which undergoes extensive reorganization, are undoubtedly the central themes of meiosis. Despite rapid progress in understanding meiosis, the complex interplay between chromatin organization and meiotic processes remains largely unexplored. In particular, the progress in understanding mammalian meiosis has lagged far behind meiotic studies in other model organisms, due to several critical barriers, including high cost, long duration, and the lack of sequence conservation of many meiosis-specific proteins across distant species. To overcome these roadblocks, we have developed cost-effective genomics and proteomics approaches to systematically identify a large number of uncharacterized mammalian meiosis factors. The current application will utilize an innovative combination of genetic, cell biological, and biochemical approaches to determine the role of our newly identified novel/uncharacterized factors and their interacting proteins in regulating meiotic recombination in mice. The proposed studies will focus on mechanistic insights into the regulation of meiotic recombination in three largely unknown or poorly understood aspects: second end capture, crossover formation, and homologous chromosome segregation. Progression through meiosis is a critical barrier to in vitro derivation of germ cells and a robust cell culture system for in vitro meiosis in multicellulr organisms remains elusive. Therefore, using a unique GFP reporter to monitor progression of meiosis in vitro, we plan to interrogate culture parameters in a stepwise manner to develop a cell culture-based in vitro meiosis system. Undoubtedly, development of an in vitro system for mammalian meiosis will not only drive basic mechanistic research on meiosis but also revolutionize regenerative medicine in the treatment of male infertility in humans.



项目成果

The ssDNA-binding protein MEIOB acts as a dosage-sensitive regulator of meiotic recombination.

单链 DNA 结合蛋白 MEIOB 作为减数分裂重组的剂量敏感调节剂

• DOI: 10.1093/nar/gkaa1016
• 发表时间: 2020-12-02
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Guo R;Xu Y;Leu NA;Zhang L;Fuchs SY;Ye L;Wang PJ
• 通讯作者: Wang PJ

A rat H1t-GFP transgene recapitulates endogenous H1t expression pattern in mouse.

大鼠 H1t-GFP 转基因重现了小鼠内源性 H1t 表达模式。

• DOI: 10.1002/dvg.23355
• 发表时间: 2020
• 期刊: Genesis (New York, N.Y. : 2000)
• 作者: Lipschutz,Emma;Dasgupta,Anindya;Guan,Yongjuan;Kistler,WStephen;Wang,PJeremy
• 通讯作者: Wang,PJeremy