PT - JOURNAL ARTICLE AU - Cuie Chen AU - Ryan Cummings AU - Aghapi Mordovanakis AU - Alan J. Hunt AU - Michael Mayer AU - David Sept AU - Yukiko M. Yamashita TI - Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division AID - 10.1101/229047 DP - 2017 Jan 01 TA - bioRxiv PG - 229047 4099 - http://biorxiv.org/content/early/2017/12/04/229047.short 4100 - http://biorxiv.org/content/early/2017/12/04/229047.full AB - Asymmetric stem cell division is a critical mechanism for balancing self-renewal and differentiation. Adult stem cells often orient their mitotic spindle to place one daughter inside the niche and the other outside of it to achieve asymmetric division. It remains unknown whether and how the niche may direct division orientation. Here we discover a novel and evolutionary conserved mechanism that couples cell polarity to cell fate. We show that the cytokine receptor homolog Dome, acting downstream of the niche-derived ligand Upd, directly binds to the microtubule-binding protein Eb1 to regulate spindle orientation in Drosophila male germline stem cells (GSCs). Dome’s role in spindle orientation is entirely separable from its known function in self-renewal mediated by the JAK-STAT pathway. We propose that integration of two functions (cell polarity and fate) in a single receptor is a key mechanism to ensure an asymmetric outcome following cell division.