title: Heritable imprinting defect caused by epigenetic abnormalities in mouse spermatogonial stem cells.
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.
authors.affiliation: Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Lee
authors.forename: Mito
authors.initials: M
authors.lastname: Kanatsu-Shinohara
authors.forename: Narumi
authors.initials: N
authors.lastname: Ogonuki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Miki
authors.forename: Kimiko
authors.initials: K
authors.lastname: Inoue
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morimoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Morimoto
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.forename: Takashi
authors.initials: T
authors.lastname: Shinohara
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D018392:Genomic Imprinting / Q000502:physiology*; D005854:Germ Cells / Q000166:cytology / Q000502:physiology*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013091:Spermatogenesis / Q000502:physiology*
chemical_list: D006657:Histones