Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the PPARγ-homolog Eip75B in Drosophila

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Abstract

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 (JH) 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, 20HE titer in ovaries and hemolymph are increased and act on nearby midgut progenitors inducing Ecdysone-induced-protein-75B (Eip75B). Strikingly, the PPARγ-homologue Eip75B drives ISC daughter cells towards absorptive enterocyte lineage ensuring epithelial growth. 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 signaling by promoting postmitotic fate when local signaling is deteriorated.

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All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided in a separate Excel File.

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Lisa Zipper

Institute of Genetics, Heinrich-Heine-Universitaet, Düsseldorf, Germany

Competing interests
The authors declare that no competing interests exist.
Denise Jassmann

Institute of Genetics, Heinrich-Heine-Universitaet, Düsseldorf, Germany

Competing interests
The authors declare that no competing interests exist.
Sofie Burgmer

Institute of Genetics, Heinrich-Heine-Universitaet, Düsseldorf, Germany

Competing interests
The authors declare that no competing interests exist.
Bastian Görlich

Institute of Genetics, Heinrich-Heine-Universitaet, Düsseldorf, Germany

Competing interests
The authors declare that no competing interests exist.
Tobias Reiff

Institute of Genetics, Heinrich-Heine-Universitaet, Düsseldorf, Germany

For correspondence
reifft@hhu.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6610-6148

Funding

Deutsche Forschungsgemeinschaft (RE 34532-1)

Tobias Reiff

Wilhelm Sander-Stiftung (2018.145.1)

Lisa Zipper

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.