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标题： Transcriptome Profile of Human Folliculogenesis

讲者：张曜耀

单位：北京大学第三医院

关键词：

Folliculogenesis RNA-Seq oocytes granulosa cells

播放： 945

论文摘要： Purpose:
Human folliculogenesis is a remarkably complex, well-orchestrated process that relies on synchronization between oocyte maturation and proliferation of the neighboring granulosa cells (GCs). However, the transcription dynamics and key events involved in folliculogenesis were unclear. This study was designed to investigate the transcriptional dynamics of the key stages of folliculogenesis.

Material and methods:
Human follicles were isolated from fresh ovarian tissues. Then oocyte and GCs were separated from oocyte-GCs complex. Follicular stages were classified according to the criteria described by Gougeon (Gougeon, 1986). The diameters of follicles and oocytes were measured in a light microscope. The oocytes and GCs that were isolated from follicles were analyzed by RNA-Seq.

Results:
We characterized the global transcriptome of human oocytes and corresponding GCs spanning five follicular stages. The oocytes and GCs exhibited distinct transcriptional process. We analyzed the gene expression patterns of the oocyte and GC clusters and found that NOL4 and CTCTF as the two top highly expressed genes in oocytes. ZEB2 and CD44 as the two top highly expressed genes in GCs. These genes derived from oocyte and GCs could be potentially used as the candidate cell type-specific markers.
We identified stage-specific genes for human oocytes and GCs that were exclusively pertained to the individual stage of folliculogenesis. These genes could be regarded as the markers of each follicular stage.
We identified 61 secretory protein-coding genes that were exclusively pertained to either oocytes or GCs and were expressed either at early or at more advanced stages of follicular development. Further evaluation of their expression levels in the biological fluids may contribute to the development of novel biomarkers for ovarian reserve in clinical application.
We analyzed the expression of the components (ligands, receptors and target genes) of key cell signaling pathways including NOTCH, TGF-β, KITLG-KIT signaling pathway and gap junctions. It showed that human folliculogenesis is coordinated by both autocrine and paracrine signaling pathways that could be initiated by either the oocytes or GCs.

Conclusion:
This work revealed unique features in transcriptional machinery and reciprocal interactions between human oocytes and GCs as well as gene signatures in each follicular stage. These identified candidate compartment-specific and stage-specific genes in both oocytes and GCs may provide a valuable clue for future functional studies. These findings may have important implication for the development of essential genetic tools for cell type-specific or stage-specific labeling and manipulations, which could be utilized in basic and translational research of the human ovary.