| Oocyte development is the basic reproductive process of female mammals,which is the basis of subsequent fertilization and embryo development.The oocyte grows and matures in the follicle and is the core cell in the follicle.Follicular development is a complex process,from follicle formation to follicle development and maturation and smooth ovulation largely depends on the communication and cooperation between oocytes and granulosa cells in the follicle.Epigenetic regulation plays an important role in follicle development,including histone modification and DNA methylation.Enhancer regulatory elements can cis-regulate intracellular gene expression.The relationship between epigenetic modifications and enhancers is very tight.Epigenetic modifications can affect the interaction between enhancers and DNA,and they are jointly involved in regulating gene expression.Granulosa cells in the follicle have a significant effect on oocyte development at the transcriptional level,so the exploration of their gene expression may be a new method and idea for studying oocyte development.Enhancers play a crucial role in the transcriptional regulation of granulosa cells.However,the expression of enhancer regulated genes in granulosa cells and their effects on oocyte development need to be further explored.Further study on the epigenetic modifications and enhancer effects on gene expression during follicular development will help to understand the factors affecting female reproductive ability and provide theoretical basis for the study of related diseases.In this study,we first explored the epigenetic and gene expression characteristics of mouse oocytes based on multi-omics data,then explored the enhancer regulatory characteristics of granulosa cells,and screened out the important genes in granulosa cells.Finally,we mined the feature interaction pairs based on the cell communication between oocytes and granulosa cells in different periods,and conducted cross-species comparisons between human and mouse.The specific contents and results of this paper are as follows:1.Exploration of epigenetic and gene expression profiles in oocytes.Transcription factors related to oocyte development stages and core genes such as Mtmr14,Arhgdia and Fzr1 were found,and the gene co-expression network and transcriptional regulatory network during oocyte development were constructed.2.Exploration of epigenetic and enhancer regulatory features in granulosa cells.Important factors related to oocyte development were identified,including genes regulated by enhancers,transcription factors highly enriched at enhancers,and genes regulated by conserved enhancers.In particular,this paper proposed a transcriptional regulation model with NR5A2 as the core,which was activated by enhancers and was also a core transcription factor that bound to enhancers to regulate the expression of other genes.3.Construction of cell communication landscape in follicles and comparative analysis across species.We revealed the gene expression characteristics and intercellular interactions in ovarian,and focused on the communication network between granulosa cells and oocytes.By cross-species analysis combined with immunohistochemistry,we explored the cell type similarities in human and mouse ovaries and found that the expression patterns of NR5A2,SF1 and ID3 were conserved in human and mouse ovaries.In summary,this study systematically analyzed the epigenetic modifications and enhancer regulation of gene expression in germ cells and granulosa cells during follicle development.It was found that epigenetic modifications changed during oocyte development.In granulosa cells,epigenetic modifications and enhancers work in fine coordination,and transcription factors bind to specific sites of enhancers to jointly regulate downstream gene expression.Granulosa cells and oocytes communicate through ligands and receptors to ensure orderly oocyte development.Based on the above conclusions,this study explored the feature gene affecting oocyte development in many aspects,and provided ideas for the study of reproductive development related diseases. |
