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Lsd1 Restricts the Number of Germline Stem Cells by Regulating Multiple Targets in Escort Cells


The mechanisms that govern the formation, size and signaling output of in vivo niches remain poorly understood. Studies of Drosophila germline stem cells (GSCs) have suggested that chromatin programming greatly influences the behavior of these cells and their progeny. Previous work has shown that loss of the highly conserved histone demethylase Lsd1 results in ectopic niche signaling and an expanded GSC phenotype. To determine direct regulatory targets of Lsd1, we employed chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) using specific cell populations inside and outside of the GSC niche. These experiments revealed that Lsd1 exhibits highly enriched binding to over one hundred genomic sites within a specific cell population. Furthermore, mis-regulation of some of these direct targets contributes to the expanded stem cell phenotype observed in Lsd1 mutants. These results provide insights into how Lsd1 directly restricts the size of the GSC microenvironment and establish a platform for understanding and exploring chromatin programming inside and outside an in vivo stem cell niche.


Vyšlo v časopise: Lsd1 Restricts the Number of Germline Stem Cells by Regulating Multiple Targets in Escort Cells. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004200
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004200

Souhrn

The mechanisms that govern the formation, size and signaling output of in vivo niches remain poorly understood. Studies of Drosophila germline stem cells (GSCs) have suggested that chromatin programming greatly influences the behavior of these cells and their progeny. Previous work has shown that loss of the highly conserved histone demethylase Lsd1 results in ectopic niche signaling and an expanded GSC phenotype. To determine direct regulatory targets of Lsd1, we employed chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) using specific cell populations inside and outside of the GSC niche. These experiments revealed that Lsd1 exhibits highly enriched binding to over one hundred genomic sites within a specific cell population. Furthermore, mis-regulation of some of these direct targets contributes to the expanded stem cell phenotype observed in Lsd1 mutants. These results provide insights into how Lsd1 directly restricts the size of the GSC microenvironment and establish a platform for understanding and exploring chromatin programming inside and outside an in vivo stem cell niche.


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