Sertoli cell-only phenotype and scRNA-seq define PRAMEF12 as a factor essential for spermatogenesis in mice

• Published in: Nature communications Vol. 10; no. 1; pp. 5196 - 18
• Main Authors: Wang, Zhengpin, Xu, Xiaojiang, Li, Jian-Liang, Palmer, Cameron, Maric, Dragan, Dean, Jurrien
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.11.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/51; 14; 14/19; 38; 38/91; 631/136/2434/1822; 631/136/532; Ablation; Animals; Antigens; Disruption; Gene expression; Genes; Humanities and Social Sciences; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Maintenance; Male; Melanoma; Mice; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Phenotype; Phenotypes; Science; Science (multidisciplinary); Sequence Analysis, RNA; Sertoli Cells - cytology; Sertoli Cells - metabolism; Spermatogenesis; Spermatogonia; Spermatogonia - cytology; Spermatogonia - metabolism; Spermatozoa; Stem cell transplantation; Stem cells; Sterility; Transcription; Tubules
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13193-3

Spermatogonial stem cells (SSCs) have the dual capacity to self-renew and differentiate into progenitor spermatogonia that develop into mature spermatozoa. Here, we document that preferentially expressed antigen of melanoma family member 12 (PRAMEF12) plays a key role in maintenance of the spermatogenic lineage. In male mice, genetic ablation of Pramef12 arrests spermatogenesis and results in sterility which can be rescued by transgenic expression of Pramef12 . Pramef12 deficiency globally decreases expression of spermatogenic-related genes, and single-cell transcriptional analysis of post-natal male germline cells identifies four spermatogonial states. In the absence of Pramef12 expression, there are fewer spermatogonial stem cells which exhibit lower expression of SSC maintenance-related genes and are defective in their ability to differentiate. The disruption of the first wave of spermatogenesis in juvenile mice results in agametic seminiferous tubules. These observations mimic a Sertoli cell-only syndrome in humans and may have translational implications for reproductive medicine. Spermatogonial stem cells have the dual capacity to self-renew and differentiate into mature spermatozoa. Here, using transcriptome analyses of juvenile testes in gene-edited mice, the authors demonstrate that PRAMEF12 is required to maintain germ cell homeostasis and promote their differentiation.