Abstract
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.
Highlights
Asymmetric cell division is a key mechanism to generate diversity in cell dates.Many stem cells utilize asymmetric cell division to balance stem cell self-renewal and differentiation
To begin to address the potential role of the niche signaling in the oriented stem cell divisions in Drosophila germline stem cells (GSCs), we first examined whether the JAK-STAT pathway components [upd, dome, hop (JAK kinase), stat92E (STAT)] might regulate GSC centrosome/spindle orientation in addition to their known role in supporting GSC self-renewal
We initially focused on day 4 after induction of RNAi, when downregulation of STAT is clear but GSC loss is incomplete
Summary
Asymmetric cell division is a key mechanism to generate diversity in cell dates. Many stem cells utilize asymmetric cell division to balance stem cell self-renewal and differentiation. Despite the clear need of coordinating the niche and stem cell polarity, it remains poorly understood whether and how the stem cell niche may regulate the stem cell polarity. This is largely due to technical difficulties to study stem cell polarity when the stem cell niche function is compromised: if stem cell niche function is perturbed, stem cell population is rapidly lost, leaving no stem cells in which the orientation can be examined
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