Chen Yongzhe, Liu Bang, Tao Sisi, Liu Lvjun, Gao Jianxin, Liang Ying, Dong Weilei, Zhou Dai
Gynecology and Obstetrics and Reproductive Medical Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
MOE Key Lab of Rare Pediatric Diseases, University of South China, Hengyang, Hunan 421001, China.
Stem Cells Int. 2025 Apr 24;2025:2362489. doi: 10.1155/sci/2362489. eCollection 2025.
Spermatogonial stem cells (SSCs) are essential for the initiation and continuation of spermatogenesis, a process fundamental to male fertility. Despite extensive studies on mouse SSCs, the mechanisms governing self-renewal and differentiation in human SSCs remain to be elucidated. This study investigated the regulatory mechanisms of SSCs by analyzing single-cell sequencing data from the GEO dataset of human testis. Analysis revealed dominant expression of CITED2 in human SSCs. Reduction of CITED2 levels in hSSC lines significantly inhibited proliferation and increased apoptosis. Protein interaction prediction and immunoprecipitation identified interactions between CITED2 and EP300 in SSC lines. RNA sequencing results indicated that CITED2 knockdown significantly affected the MAPK pathway and the HSPA6 gene. Overexpression of HSPA6 mitigated the proliferative and apoptotic changes provoked by CITED2 downregulation. These findings provide novel insights into the regulatory and functional mechanisms of CITED2-mediated hSSC development.
精原干细胞（SSCs）对于精子发生的启动和持续至关重要，而精子发生是男性生育能力的基础过程。尽管对小鼠精原干细胞进行了广泛研究，但人类精原干细胞自我更新和分化的调控机制仍有待阐明。本研究通过分析来自人类睾丸GEO数据集的单细胞测序数据，探究了精原干细胞的调控机制。分析显示CITED2在人类精原干细胞中占主导表达。降低hSSC系中CITED2的水平显著抑制增殖并增加凋亡。蛋白质相互作用预测和免疫沉淀确定了SSC系中CITED2与EP300之间的相互作用。RNA测序结果表明，CITED2基因敲低显著影响丝裂原活化蛋白激酶（MAPK）信号通路和HSPA6基因。HSPA6的过表达减轻了CITED2下调引起的增殖和凋亡变化。这些发现为CITED2介导的人类精原干细胞发育的调控和功能机制提供了新见解。
