RRC ID 11972
Author Takashima S, Takehashi M, Lee J, Chuma S, Okano M, Hata K, Suetake I, Nakatsuji N, Miyoshi H, Tajima S, Tanaka Y, Toyokuni S, Sasaki H, Kanatsu-Shinohara M, Shinohara T.
Title Abnormal DNA methyltransferase expression in mouse germline stem cells results in spermatogenic defects.
Journal Biol Reprod
Abstract Although spermatogonial stem cells (SSCs) are committed to spermatogenesis, they may also convert to an embryonic stem cell-like pluripotent state at a low frequency. Because changes in DNA methylation patterns are associated with this conversion, we examined the effect of manipulating DNA methyltransferase (Dnmt) expression on the fate of cultured SSCs, germline stem (GS) cells. Dnmt1 knockdown induced apoptosis in GS cells, which was attenuated by the loss of Trp53. In contrast, GS cells proliferated normally in vitro after Dnmt3a/Dnmt3b ablation or during Dnmt3l overexpression. However, Dnmt3a/Dnmt3b double-mutant cells showed hypomethylation in the SineB1 repetitive sequence, and Dnmt3l-overexpressing cells showed hypermethylation in major and minor satellite sequences; neither cell type formed teratomas and completed spermatogenesis following transplantation into the seminiferous tubules. Although genetic manipulation did not increase the conversion of GS cells to a pluripotent state, these results underscore the important role of DNMTs in survival and spermatogenic differentiation in SSCs.
Volume 81(1)
Pages 155-64
Published 2009-7-1
DOI 10.1095/biolreprod.108.074708
PII biolreprod.108.074708
PMID 19228594
MeSH Animals Apoptosis / genetics Cells, Cultured DNA (Cytosine-5-)-Methyltransferases / genetics* DNA (Cytosine-5-)-Methyltransferases / metabolism Gene Expression Regulation, Enzymologic Germ Cells / enzymology Germ Cells / metabolism* Infertility, Male / genetics Male Mice Mice, Knockout Spermatogenesis / genetics* Spermatozoa / abnormalities Spermatozoa / enzymology Spermatozoa / metabolism Stem Cells / enzymology Stem Cells / metabolism* Stem Cells / physiology
IF 3.322
Times Cited 48
DNA material AxCANCre (RDB01748)