PT  - JOURNAL ARTICLE
AU  - Lisa Zipper
AU  - Denise Jassmann
AU  - Bastian Görlich
AU  - Tobias Reiff
TI  - Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the <em>PPARγ</em>-homologue <em>E75B</em> in <em>Drosophila</em>
AID  - 10.1101/2020.02.24.962829
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.24.962829
4099  - http://biorxiv.org/content/early/2020/02/26/2020.02.24.962829.short
4100  - http://biorxiv.org/content/early/2020/02/26/2020.02.24.962829.full
AB  - Developmental studies revealed fundamental principles on how organ size and function is achieved, but less is known about organ adaptation to new physiological demands. In fruit flies, juvenile hormone induces intestinal stem cell (ISC) driven absorptive epithelial expansion balancing energy uptake with increased energy demands of pregnancy.Here, we show 20-Hydroxy-Ecdysone (20HE)-signaling controlling organ homeostasis with physiological and pathological implications. Upon mating, ovarian 20HE acts on nearby midgut progenitors inducing Ecdysone-induced-protein-75B (E75B). Strikingly, the PPARγ-homologue E75B restricts ISC daughter cell differentiation towards absorptive enterocyte lineage ensuring epithelial growth even in the absence of local fate determining Notch. To our knowledge, this is the first time a systemic hormone is shown to direct local stem cell fate decisions. Given the protective, but mechanistically unclear role of steroid hormones in female colorectal cancer patients, our findings suggest a tumor-suppressive role for steroidal signalling by promoting postmitotic fate independent of deteriorated local signalling.