期刊
CELL DEATH DISCOVERY
卷 8, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41420-022-01139-6
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类别
资金
- Ministry of Science and Technology [2018YFA0801100]
- National Science Foundation of China [31630091, 31871185]
- Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD)
- National Center for International Research [2017B01012]
This study discovered the crucial role of the CT47 gene family in human-specific spermatogenesis. CT47 inhibits spermatogenesis by stabilizing PRMT5 and interacting with its accumulation in the nucleus. Testosterone decreases the nuclear concentration of CT47/PRMT5 and promotes spermatocyte progression. Loss of CT47 in human embryonic stem cells prevents the testosterone-induced increase in haploid cells.
Exploring the functions of human-specific genes (HSGs) is challenging due to the lack of a tractable genetic model system. Testosterone is essential for maintaining human spermatogenesis and fertility, but the underlying mechanism is unclear. Here, we identified Cancer/Testis Antigen gene family 47 (CT47) as an essential regulator of human-specific spermatogenesis by stabilizing arginine methyltransferase 5 (PRMT5). A humanized mouse model revealed that CT47 functions to arrest spermatogenesis by interacting with and regulating CT47/PRMT5 accumulation in the nucleus during the leptotene/zygotene-to-pachytene transition of meiosis. We demonstrate that testosterone induces nuclear depletion of CT47/PRMT5 and rescues leptotene-arrested spermatocyte progression in humanized testes. Loss of CT47 in human embryonic stem cells (hESCs) by CRISPR/Cas9 led to an increase in haploid cells but blocked the testosterone-induced increase in haploid cells when hESCs were differentiated into haploid spermatogenic cells. Moreover, CT47 levels were decreased in nonobstructive azoospermia. Together, these results established CT47 as a crucial regulator of human spermatogenesis by preventing meiosis initiation before the testosterone surge.
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