Journal Article

pigenetic modifications and self-renewal regulation of ~ouse germline stem cells

Jiyoung Lee Takashi Shinohara

2011

Overview

Germline stem （GS） cells were established from gonocytes and spermatogonia of postnatal mouse testes. GS cells proliferate in the presence of several kinds of cytokines, and a small percentage of GS cells also show spermatogonial stem cell （SSC） activity, i.e., they differentiate into sperm after being transplanted into infertile mouse testes without endogenous spermatogenesis. Interestingly, in GS cell culture, we also found that pluripotent stem cells （multipotent germline stem cells （mGS cells）） could be derived and these mGS cells do not have normal androgenetic genomic im- printing marks that are shown in GS cells, e.g., H19 hypermethylation. A new culture system for fetal male germ cells （embryonic GS （eGS） cells） has also been recently developed. Although these cells exhibited SSC potential, the offspring from cultured cells showed heritable imprinting defects in their DNA methylation patterns. In an attempt to understand the self-renewal machinery in SSCs, we transfected H-Ras and cylin D2 into GS cells, and successfully reconstructed the SSC self-renewal ability without using exogenous cytokines. Although these cells showed SSC activity in germ cell transplantation assays, we also found development of seminomatous tumors, possibly induced by excessive self-renewing signal. These stem cell culture systems are useful tools not only for understanding the mechanisms of self-renewal or epigenetic reprogramming but also for clarifying the mechanism of germ cell tumor development.

• Subject: DNA甲基化 / 修改 / 小鼠睾丸 / 更新机制 / 生殖干细胞 / 自我更新能力 / 调控 / 雄性生殖细胞