Abstract
BackgroundGermline stem cells play an essential role in establishing the fertility of an organism. Although extensively characterized, the regulatory mechanisms that govern the fundamental properties of mammalian female germline stem cells remain poorly understood.ResultsWe generate genome-wide profiles of the histone modifications H3K4me1, H3K27ac, H3K4me3, and H3K27me3, DNA methylation, and RNA polymerase II occupancy and perform transcriptome analysis in mouse female germline stem cells. Comparison of enhancer regions between embryonic stem cells and female germline stem cells identifies the lineage-specific enhancers involved in germline stem cell features. Additionally, our results indicate that DNA methylation primarily contributes to female germline stem cell unipotency by suppressing the somatic program and is potentially involved in maintenance of sexual identity when compared with male germline stem cells. Moreover, we demonstrate down-regulation of Prmt5 triggers differentiation and thus uncover a role for Prmt5 in maintaining the undifferentiated status of female germline stem cells.ConclusionsThe genome-wide epigenetic signatures and the transcription regulators identified here provide an invaluable resource for understanding the fundamental features of mouse female germline stem cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1023-z) contains supplementary material, which is available to authorized users.
Highlights
Germline stem cells play an essential role in establishing the fertility of an organism
We found that Dazl and Stella are expressed in female germline stem cell (FGSC) (Additional file 1: Figure S1b)
In contrast to Nanog and Sox2, which are expressed in embryonic stem cell (ESC), we found that Ifitm3/Fragilis, Ptx3, and GM1673 are selectively expressed in FGSCs (Fig. 1b)
Summary
Germline stem cells play an essential role in establishing the fertility of an organism. Zhang et al Genome Biology (2016): specific transcription factors, genome-wide epigenetic modifications are actively involved in development and cell fate determination, which constitute another layer of regulation beyond the genome sequence. Identifying and characterizing regulatory DNA elements (e.g., promoters and enhancers) is hugely difficult due to the lack of recognizable and consistent sequence features but epigenetic profiling in ESCs has proven that it is a powerful tool to delineate these. These profiling analyses provide insights into the understanding of stem cell biology
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