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

Zhengpin Wang (), Xiaojiang Xu, Jian-Liang Li, Cameron Palmer, Dragan Maric and Jurrien Dean ()
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Zhengpin Wang: NIDDK, National Institutes of Health
Xiaojiang Xu: National Institutes of Health
Jian-Liang Li: National Institutes of Health
Cameron Palmer: NIDDK, National Institutes of Health
Dragan Maric: National Institutes of Health
Jurrien Dean: NIDDK, National Institutes of Health

Nature Communications, 2019, vol. 10, issue 1, 1-18

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-13193-3

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