RRC ID 11778
Author Lee J, Kanatsu-Shinohara M, Ogonuki N, Miki H, Inoue K, Morimoto T, Morimoto H, Ogura A, Shinohara T.
Title Heritable imprinting defect caused by epigenetic abnormalities in mouse spermatogonial stem cells.
Journal Biol Reprod
Abstract Male germ cells undergo dynamic epigenetic reprogramming during fetal development, eventually establishing spermatogonial stem cells (SSCs) that can convert into pluripotent stem cells. However, little is known about the developmental potential of fetal germ cells and how they mature into SSCs. We developed a culture system for fetal germ cells that proliferate for long periods of time. Male germ cells from embryos 12.5-18.5 days postcoitum could expand by glial cell line-derived neurotrophic factor, a self-renewal factor for SSCs. These cells did not form teratomas, but repopulated seminiferous tubules and produced spermatogenesis, exhibiting spermatogonia potential. However, the offspring from cultured cells showed growth abnormalities and were defective in genomic imprinting. The imprinting defect persisted in both the male and female germlines for at least four generations. Moreover, germ cells in the offspring showed abnormal histone modifications and DNA methylation patterns. These results indicate that fetal germ cells have a limited ability to become pluripotent cells and lose the ability to undergo epigenetic reprogramming by in vitro culture.
Volume 80(3)
Pages 518-27
Published 2009-3-1
DOI 10.1095/biolreprod.108.072330
PII biolreprod.108.072330
PMID 19020300
MeSH Animals Body Weight / genetics Body Weight / physiology Cells, Cultured DNA Methylation Embryonic Stem Cells / cytology Embryonic Stem Cells / physiology* Epigenesis, Genetic / physiology* Genomic Imprinting / physiology* Germ Cells / cytology Germ Cells / physiology* Histones / genetics Histones / metabolism Male Mice Mice, Inbred ICR Spermatogenesis / physiology*
IF 3.322
Times Cited 29
WOS Category REPRODUCTIVE BIOLOGY
Resource
Mice RBRC00639