Transcriptomic diversification of developing cumulus and mural granulosa cells in mouse ovarian follicles.
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 ∼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.
The Jackson Laboratory, Bar Harbor, Maine.
Karen
K
Wigglesworth
Department of Biology Education, College of Education, Chonnam National University, Buk-gu, Gwangju, Korea.
Kyung-Bon
KB
Lee
Laboratory of Applied Genetics, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
Chihiro
C
Emori
Laboratory of Applied Genetics, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
Koji
K
Sugiura
The Jackson Laboratory, Bar Harbor, Maine john.eppig@jax.org.
John J
JJ
Eppig
D000465:Algorithms; D000818:Animals; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006107:Granulosa Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009865:Oocytes / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism; D059467:Transcriptome
cumulus cells; mouse; mural granulosa cells; oocyte; oocyte-derived paracrine factors; ovarian follicle; transcriptome