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‘Sertoli cell-only’ phenotype and single-cell RNA-seq define PRAMEF12 as a germline-specific factor for male stem cell maintenance and differentiation [scRNA-seq]

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) is a key regulator of germline stem cell maintenance and differentiation. 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 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 junenile mice results in agametic seminiferous tubules. These observations mimic a ‘Sertoli cell-only’ phenotype in humans and may have translational implications for reproductive medicine.

ORGANISM(S): Mus musculus

PROVIDER: GSE117707 | GEO | 2019/10/22

REPOSITORIES: GEO

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‘Sertoli cell-only’ phenotype and single-cell RNA-seq define PRAMEF12 as a germline-specific factor for male stem cell maintenance and differentiation [RNA-Seq]

Project description: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) is a key regulator of germline stem cell maintenance and differentiation. 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 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 junenile mice results in agametic seminiferous tubules. These observations mimic a ‘Sertoli cell-only’ phenotype in humans and may have translational implications for reproductive medicine.

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