染色质
生物
细胞生物学
精子发生
干细胞
生殖系
舱室(船)
转录因子
核糖核酸
男性不育
抑制因子
生殖细胞
细胞
抄写(语言学)
遗传学
基因
不育
内分泌学
怀孕
哲学
地质学
海洋学
语言学
作者
Sara Di Persio,Tobias Tekath,Lara Marie Siebert-Kuss,Jann‐Frederik Cremers,Joachim Wistuba,Xin Li,Gerd Meyer zu Hörste,Hannes C.A. Drexler,Margot J. Wyrwoll,Frank Tüttelmann,Martin Dugas,Sabine Kliesch,Stefan Schlatt,Sandra Laurentino,Nina Neuhaus
标识
DOI:10.1016/j.xcrm.2021.100395
摘要
Despite the high incidence of male infertility, only 30% of infertile men receive a causative diagnosis. To explore the regulatory mechanisms governing human germ cell function in normal and impaired spermatogenesis (crypto), we performed single-cell RNA sequencing (>30,000 cells). We find major alterations in the crypto spermatogonial compartment with increased numbers of the most undifferentiated spermatogonia (PIWIL4+). We also observe a transcriptional switch within the spermatogonial compartment driven by increased and prolonged expression of the transcription factor EGR4. Intriguingly, the EGR4-regulated chromatin-associated transcriptional repressor UTF1 is downregulated at transcriptional and protein levels. This is associated with changes in spermatogonial chromatin structure and fewer Adark spermatogonia, characterized by tightly compacted chromatin and serving as reserve stem cells. These findings suggest that crypto patients are disadvantaged, as fewer cells safeguard their germline's genetic integrity. These identified spermatogonial regulators will be highly interesting targets to uncover genetic causes of male infertility.
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