Estrogen-Related Receptor is Required in Adult Females for Germline Stem Cell Maintenance.

Stem cell self-renewal and proper tissue function rely on conserved metabolic regulators to balance energy production with inter-organ metabolic trafficking. The estrogen-related receptor (ERR) subfamily of orphan nuclear receptors are major transcriptional regulators of metabolism. In mammals, ERRs have roles in regulating mitochondrial biosynthesis, lipid metabolism, as well as stem cell maintenance. The sole ortholog promotes larval growth by establishing a metabolic state during the latter half of embryogenesis. In addition, is required in adult males to coordinate glycolytic metabolism with lipid synthesis and within the testis to regulate spermatogenesis gene expression and fertility. Despite extensive work characterizing of the role of in metabolism, whether has a conserved requirement in regulating stem cell behavior has been understudied. To determine whether ERR regulates stem cell activity in , we used the established adult female germline stem cell (GSC) lineage as a model. We found that whole-body knockout in adult females using conditional heat shock-driven FLP-FRT recombination significantly reduces egg production and decreases GSC number. In addition, we found that ERR activity is required cell-autonomously in the adult female germline for maintenance of GSCs; whereas ERR regulation of GSCs is independent of its activity in adult female adipocytes. Our results highlight an ancient and conserved role for in the regulation of stem cell self-renewal.