The histone methyltransferase ESET is required for the survival of spermatogonial stem/progenitor cells in mice

作者：Junhui An, Xiaoying Zhang, Jinzhou Qin, Yi Wan, Yiping Hu, Tianrun Liu, Jingrui Li, Wuzi Dong, Enqi Du, Chuanying Pan, Wenxian Zeng · 发表于：Cell Death and Disease · 年份：2014 · DOI：10.1038/cddis.2014.171 · 被引用次数：46 · 研究领域：Sperm and Testicular Function、Epigenetics and DNA Methylation、Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Self-renewal and differentiation of spermatogonial stem cells (SSCs) are the foundation of spermatogenesis throughout a male's life. SSC transplantation will be a valuable solution for young male patients to preserve their fertility. As SSCs in the collected testis tissue from the patients are very limited, it is necessary to expansion the SSCs in vitro. Previous studies suggested that histone methyltransferase ERG-associated protein with SET domain (ESET) represses gene expression and is essential for the maintenance of the pool of embryonic stem cells and neurons. The objective of this study was to determine the role of ESET in SSCs using in vitro cell culture and germ cell transplantation. Cell transplantation assay showed that knockdown of ESET reduced the number of seminiferous tubules with spermatogenesis when compared with that of the control. Knockdown of ESET also upregulated the expression of apoptosis-associated genes (such as P53, Caspase9, Apaf1), whereas inhibited the expression of apoptosis-suppressing genes (such as Bcl2l1, X-linked inhibitor of apoptosis protein). In addition, suppression of ESET led to increase in expression of Caspase9 and activation of Caspase3 (P17) as well as cleavage of poly (ADP-ribose) polymerase. Among the five ESET-targeting genes (Cox4i2, spermatogenesis and oogenesis Specific Basic Helix-Loop-Helix 2, Nobox, Foxn1 and Dazl) examined by ChIP assay, Cox4i2 was found to regulate SSC apoptosis by the rescue experiment. BSP analyses fu...