ABSTRACT
In the rapidly moving field of stem cell and embryo research, research questions often sit at the intersection of scientific inquiry and ethical considerations. The International Society for Stem Cell Research (ISSCR) produces guidelines to help navigate decisions in this area. For Cell's 50th Anniversary Focus on Developmental Biology, scientific editor Sarah Geisler discussed the importance of the ISSCR guidelines on stem cell and embryo research for both the stem cell community and the broader public with Amander Clark, Robin Lovell-Badge, and Janet Rossant, who have been involved in the ongoing evolution of the guidelines. A lightly edited transcript of their conversation is shared here.
Subject(s)
Embryo Research , Societies, Scientific , Stem Cell Research , Humans , Stem Cell Research/ethics , Embryo Research/ethics , Guidelines as TopicABSTRACT
The transcription factor FOXL2 is required in ovarian somatic cells for female fertility. Differential timing of Foxl2 deletion, in embryonic versus adult mouse ovary, leads to distinctive outcomes, suggesting different roles across development. Here, we comprehensively investigated FOXL2's role through a multi-omics approach to characterize gene expression dynamics and chromatin accessibility changes, coupled with genome-wide identification of FOXL2 targets and on-chromatin interacting partners in somatic cells across ovarian development. We found that FOXL2 regulates more targets postnatally, through interaction with factors regulating primordial follicle formation and steroidogenesis. Deletion of one interactor, ubiquitin-specific protease 7 (Usp7), results in impairment of somatic cell differentiation, germ cell nest breakdown, and ovarian development, leading to sterility. Our datasets constitute a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.