GSE131656
Unique Epigenetic Programming Distinguishes Regenerative Spermatogonial Stem Cells in the Developing Mouse Testis (ChIP-seq)
Background: Spermatogonial stem cells (SSCs) sustain the process of steady-state spermatogenesis in the mammalian testis, which is critical to the ongoing production of sperm and male fertility. SSCs can both self-renew to perpetuate the SSC population, and give rise to progenitors to propel the spermatogenic differentiation pathway. SSCs are detectable as a small subpopulation of undifferentiated spermatogonia that demonstrate regenerative capacity in a transplantation assay, and can be selectively recovered on the basis of expression of an Id4-eGfp sortable marker transgene. Enriched populations of SSCs and progenitors display consistent differences in gene expression patterns suggesting they represent discrete spermatogonial subtypes. Results: Here we describe distinct spermatogonial subtype-specific epigenetic programming profiles associated with subtype-specific differential gene expression on the basis of genome-wide patterns of six different histone modifications, chromatin accessibility, and DNA methylation. We find that similarly expressed genes show no differences in epigenetic programming, whereas differentially expressed genes show distinct histone modification patterns as well as subtype-specific differences in patterns of distal intergenic low-methylated regions. Motif-enrichment analysis of differentially programmed elements predicts a set of transcription factors that may regulate this spermatogonial subtype-specific epigenetic programming, and gene-specific chromatin immunoprecipitation analyses confirm subtype-specific differences in binding of a subset of these factors to target genes. Conclusions: Taken together, these results indicate that SSCs and progenitors are discrete spermatogonial subtypes that appear to be differentially programmed to carry out mutually exclusive functions including self-renewal and maintenance of regenerative capacity in SSCs and lineage commitment and loss of regenerative capacity in progenitors. Overall design: ChIP-seq of P6 ID4-eGFP Bright and Dim mice spermatogonia were generated by deep sequencing, in triplicate.