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

作　　者：Jiyoung Lee 

机构地区：[1]Global Center of Excellence Program, Tokyo Medical and Dental University, Tokyo 113-8510, Japan [2]PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan [3]Department of Molecular Genetics, Gradu- ate School of Medicine, Kyoto University, Kyoto 606-8501, Japan [4]CREST, JST, Japan

出　　处：《Cell Research》2011年第8期1164-1171,共8页细胞研究（英文版）

摘　　要：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.

关 键 词：germline stem cells spermatogonial stem cells SPERMATOGENESIS SELF-RENEWAL genomic imprinting 

分 类 号：Q75[生物学—分子生物学] N1[自然科学总论]