Control of ovarian stem cells by adipocytes in response to diet. Alissa Armstrong¹, Leesa Sampson¹, Kaitlin Laws¹, Robert Cole², Daniela Drummond-Barbosa¹. 1) Biochemistry and Molecular Biology, JHU School of Public Health, Baltimore, MD; 2) Mass Spectrometry and Proteomics Facility, JHU School of Medicine, Baltimore, MD.

   Adult stem cells play key roles in tissue homeostasis and damage repair; however, it is unclear how whole-body physiology influences stem cell lineages. Our past work showed that Drosophila ovarian stem cell lineages respond to diet via multiple nutrient-sensing pathways. For example, insulin-like peptides, ecdysone and Target of rapamycin (TOR) act on or within ovarian cells to control germline stem cell (GSC) maintenance and proliferation. Other adult tissues are also sensitive to diet and nutrient-sensing pathways, suggesting potential crosstalk; however, the role of multi-organ communication in the stem cell dietary response is largely unknown. Mammalian adipose tissue and the Drosophila fat body are sensitive to nutrients and have energy storage and endocrine roles; therefore, our studies focus on how nutrient sensing within adipocytes remotely impacts adult ovarian stem cells and their progeny. We find that inhibiting either insulin or TOR signaling specifically in adult adipocytes reduces GSC number and egg production. We also observe specific effects of different nutrient-sensing pathways within adipocytes on the ovary. Blocked insulin signaling in adult adipocytes increases dying vitellogenic egg chambers. In contrast, inhibiting TOR signaling within adipocytes does not affect vitellogenesis; instead, ovaries accumulate mature oocytes. These data suggest that nutrient sensing within adipocytes remotely controls ovarian stem cells and their progeny, refining their response to diet. In search of fat body factors that transmit dietary status to the ovary, we performed a quantitative proteomics comparison between the fat body from flies fed yeast-rich versus yeast-free diets, identifying over 50 putative secreted proteins altered by diet. We are currently performing functional analyses of these candidates for potential roles in oogenesis. This work will illuminate how inter-organ communication modulates adult stem cell lineages upon dietary changes.