GSE158285
RNA Helicase DDX5 Acts as a Critical Regulator for Gonocyte Survival in Neonatal Mouse
Mammalian spermatogenesis is a dynamic and highly coordinated biological process. The production of spermatozoa relies on a pool of spermatogonial stem cells (SSCs), formed in infancy from their precursor cells, the gonocytes. In this study, we found that Ddx5 is highly expressed in male germ cells from embryonic period. We generated germ-cell-specific Ddx5 knockout mice (Ddx5 cKO) by using Mvh-Cre transgenic mice. Ddx5 homozygous knockout mice resulted in significant smaller size and light weight of testes, but Ddx5 heterzygous knockout mice have no effect on reproduction. Furthermore, Ddx5 homozygous knockout resulted in gradual loss of germ cells in neonate's testes and a complete loss of germ cells within 6 days after birth, leading to azoospermia and infertility in male adults. Single cell RNA sequencing (scRNA-seq) experiments showed that the expression of genes that are involved in cell cycle and GDNF pathway were significantly decreased in gonocytes after Ddx5 knockout. Together, these results reveal critical functions of Ddx5 in the survival and cell fate determination of gonocytes. Overall design: Single cell gene expression profiling of whole testes from wild type (WT) and germ-cell-specific Ddx5 knockout mice (Ddx5 cKO) at postnatal day 2.