Unique Epigenetic Programming Distinguishes Regenerative Spermatogonial Stem Cells in the Developing Mouse Testis
Keren Cheng,
I-Chung Chen,
Ching-Hsun Eric Cheng,
Kazadi Mutoji,
Benjamin J. Hale,
Brian P. Hermann,
Christopher B. Geyer,
Jon M. Oatley,
John R. McCarrey
Affiliations
Keren Cheng
Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA
I-Chung Chen
Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA
Ching-Hsun Eric Cheng
Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA
Kazadi Mutoji
Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA
Benjamin J. Hale
Department of Anatomy and Cell Biology at the Brody School of Medicine and East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
Brian P. Hermann
Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA
Christopher B. Geyer
Department of Anatomy and Cell Biology at the Brody School of Medicine and East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
Jon M. Oatley
Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
John R. McCarrey
Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA; Corresponding author
Summary: Spermatogonial stem cells (SSCs) both self-renew and give rise to progenitors that initiate spermatogenic differentiation in the mammalian testis. Questions remain regarding the extent to which the SSC and progenitor states are functionally distinct. Here we provide the first multiparametric integrative analysis of mammalian germ cell epigenomes comparable with that done for >100 somatic cell types by the ENCODE Project. Differentially expressed genes distinguishing SSC- and progenitor-enriched spermatogonia showed distinct histone modification patterns, particularly for H3K27ac and H3K27me3. Motif analysis predicted transcription factors that may regulate spermatogonial subtype-specific fate, and immunohistochemistry and gene-specific chromatin immunoprecipitation analyses confirmed subtype-specific differences in target gene binding of a subset of these factors. Taken together, these results show that SSCs and progenitors display distinct epigenetic profiling consistent with these spermatogonial subtypes being differentially programmed to either self-renew and maintain regenerative capacity as SSCs or lose regenerative capacity and initiate lineage commitment as progenitors.
