Transcriptomic Diversification of Developing Cumulus and Mural Granulosa Cells in Mouse Ovarian Follicles
Transcriptomic Diversification of Developing Cumulus and Mural Granulosa Cells in Mouse Ovarian Follicles
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DOI：
10.1095/biolreprod.114.121756
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发表时间：
2015-01-01
影响因子：
3.6
通讯作者：
Eppig, John J.
中科院分区：
文献类型：
--
作者：
Wigglesworth, Karen;Lee, Kyung-Bon;Eppig, John J.
卵丘细胞和壁颗粒细胞（MGCs）在有腔卵泡中具有功能上不同的作用，在全球和系统水平上比较它们的转录组可以推动未来对其功能多样性机制的研究。这些细胞分别从促性腺激素刺激未成熟小鼠前后的小窦卵泡和大窦卵泡中分离。这两种细胞类型都经历了戏剧性的转录组学变化，它们之间的差异随着卵泡的生长而增加。虽然卵丘细胞的卵泡发育的两个阶段都有能力进行体外扩增，他们在其他方面显着不同的转录组的变化定量相当于MGCs。基因本体分析显示，小卵泡的卵丘细胞中富含通常与代谢过程的催化组分相关的转录物，而大卵泡的卵丘细胞则参与代谢、细胞分化和粘附的调节。卵丘细胞与MGCs的对比显示，卵丘细胞富含与代谢和细胞增殖相关的转录物，而MGCs富含参与细胞信号传导和分化的转录物。在体外和体内模型被用来测试的假设，较高水平的成绩单在卵丘细胞与MGCs的刺激卵母细胞衍生的旁分泌因子（ODPF）的结果。令人惊讶的是，卵丘细胞中48%的转录物高于MGCs，但ODPF不刺激。ODPFs刺激的细胞主要与细胞分裂、mRNA加工或代谢的催化途径有关，而ODPFs不刺激的细胞则与信号传导、转录、磷酸化或代谢调节等调节过程有关。
Cumulus cells and mural granulosa cells (MGCs) have functionally distinct roles in antral follicles, and comparison of their transcriptomes at a global and systems level can propel future studies on mechanisms underlying their functional diversity. These cells were isolated from small and large antral follicles before and after stimulation of immature mice with gonadotropins, respectively. Both cell types underwent dramatic transcriptomic changes, and differences between them increased with follicular growth. Although cumulus cells of both stages of follicular development are competent to undergo expansion in vitro, they were otherwise remarkably dissimilar with transcriptomic changes quantitatively equivalent to those of MGCs. Gene ontology analysis revealed that cumulus cells of small follicles were enriched in transcripts generally associated with catalytic components of metabolic processes, while those from large follicles were involved in regulation of metabolism, cell differentiation, and adhesion. Contrast of cumulus cells versus MGCs revealed that cumulus cells were enriched in transcripts associated with metabolism and cell proliferation while MGCs were enriched for transcripts involved in cell signaling and differentiation. In vitro and in vivo models were used to test the hypothesis that higher levels of transcripts in cumulus cells versus MGCs is the result of stimulation by oocyte-derived paracrine factors (ODPFs). Surprisingly similar to 48% of transcripts higher in cumulus cells than MGCs were not stimulated by ODPFs. Those stimulated by ODPFs were mainly associated with cell division, mRNA processing, or the catalytic pathways of metabolism, while those not stimulated by ODPFs were associated with regulatory processes such as signaling, transcription, phosphorylation, or the regulation of metabolism.