Abstract
ABSTRACTSignaling pathways and epigenetic mechanisms have both been shown to play essential roles in regulating stem cell activity. While the role of either mechanism in this regulation is well established in multiple stem cell lineages, how the two mechanisms interact to regulate stem cell activity is not as well understood. Here we report that in the Drosophila testis, an H3K4me3-specific histone demethylase encoded by little imaginal discs (lid) maintains germline stem cell (GSC) mitotic index and prevents GSC premature differentiation. Lid is required in germ cells for proper expression of the Stat92E transcription factor, the downstream effector of the Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway. Our findings support a germ cell autonomous role for the JAK-STAT pathway in maintaining GSCs and place Lid as an upstream regulator of this pathway. Our study provides new insights into the biological functions of a histone demethylase in vivo and sheds light on the interaction between epigenetic mechanisms and signaling pathways in regulating stem cell activities.
Highlights
Extrinsic signals from cells comprising the stem cell niche are essential in maintaining stem cell activity (Morrison and Spradling, 2008)
The Drosophila male germline stem cell (GSC) niche is one of the best characterized niches in which GSCs associate with two types of somatic cells: hub cells located at the tip of the testis, and cyst stem cells (CySCs) two of which surround each GSC (Fig. 1A)
These results suggest that Lid is required to maintain GSCs at the Drosophila testis niche
Summary
Extrinsic signals from cells comprising the stem cell niche are essential in maintaining stem cell activity (Morrison and Spradling, 2008). Epigenetic regulation that changes stem cell chromatin structure without altering DNA sequences acts as an important intrinsic mechanism to maintain stem cells (Eun et al, 2010). Both mechanisms are important to regulate stem cell activities, our understanding of the crosstalk between the two events is limited to a few examples (Cherry and Matunis, 2010; Eliazer et al, 2011; Tarayrah et al, 2013). Hub cells and CySCs contribute to a niche that provides the critical signaling necessary to preserve GSC identity and activity (Kiger et al, 2001; Leatherman and DiNardo, 2008, 2010; Tulina and Matunis, 2001). The intrinsic activation of Stat92E in CySCs activates BMP signaling and is thought to be sufficient to cause continuous GSC self-renewal while Stat92E in the GSCs has been reported to only regulate their adhesion to the niche (Leatherman and DiNardo, 2008, 2010)
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