Abstract
Specialized microenvironments called niches regulate tissue homeostasis by controlling the balance between stem cell self-renewal and the differentiation of stem cell daughters. However the mechanisms that govern the formation, size and signaling of in vivo niches remain poorly understood. Loss of the highly conserved histone demethylase Lsd1 in Drosophila escort cells results in increased BMP signaling outside the cap cell niche and an expanded germline stem cell (GSC) phenotype. Here we present evidence that loss of Lsd1 also results in gradual changes in escort cell morphology and their eventual death. To better characterize the function of Lsd1 in different cell populations within the ovary, we performed Chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq). This analysis shows that Lsd1 associates with a surprisingly limited number of sites in escort cells and fewer, and often, different sites in cap cells. These findings indicate that Lsd1 exhibits highly selective binding that depends greatly on specific cellular contexts. Lsd1 does not directly target the dpp locus in escort cells. Instead, Lsd1 regulates engrailed expression and disruption of engrailed and its putative downstream target hedgehog suppress the Lsd1 mutant phenotype. Interestingly, over-expression of engrailed, but not hedgehog, results in an expansion of GSC cells, marked by the expansion of BMP signaling. Knockdown of other potential direct Lsd1 target genes, not obviously linked to BMP signaling, also partially suppresses the Lsd1 mutant phenotype. These results suggest that Lsd1 restricts the number of GSC-like cells by regulating a diverse group of genes and provide further evidence that escort cell function must be carefully controlled during development and adulthood to ensure proper germline differentiation.
Highlights
Stem cells undergo self-renewing divisions in which at least one daughter retains its stem cell identity, while the second daughter may or may not differentiate, depending on intrinsic and extrinsic cues
Studies of Drosophila germline stem cells (GSCs) have suggested that chromatin programming greatly influences the behavior of these cells and their progeny
To determine direct regulatory targets of Lysine Specific Demethylase 1 (Lsd1), we employed chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) using specific cell populations inside and outside of the GSC niche
Summary
Stem cells undergo self-renewing divisions in which at least one daughter retains its stem cell identity, while the second daughter may or may not differentiate, depending on intrinsic and extrinsic cues. Drosophila female GSCs reside in a well-characterized niche at the tip of a structure called a germarium (Figure 1A). Escort cells reside adjacent to the cap cells and line the anterior portion of the germarium. These cells act to shepherd the germ cells during the earliest stages of their differentiation [3,4], after which developing germline cysts are enveloped by follicle cells derived from a second stem cell population within the germarium. Cap cells produce Decapentaplegic (Dpp), which in turn activates a canonical Bone Morphogenic Protein (BMP) signal transduction pathway in GSCs [5,6]. Ectopic Dpp signaling outside the tip of the germarium results in an expanded GSC phenotype [5,9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
