title: Epigenetic alteration of imprinted genes during neural differentiation of germline-derived pluripotent stem cells.
abstract: Spermatogonial stem cells (SSCs), which are unipotent stem cells in the testes that give rise to sperm, can be converted into germline-derived pluripotent stem (gPS) by self-induction. The androgenetic imprinting pattern of SSCs is maintained even after their reprogramming into gPS cells. In this study, we used an in vitro neural differentiation model to investigate whether the imprinting patterns are maintained or altered during differentiation. The androgenetic patterns of H19, Snrpn, and Mest were maintained even after differentiation of gPS cells into NSCs (gPS-NSCs), whereas the fully unmethylated status of Ndn in SSCs was altered to somatic patterns in gPS cells and gPS-NSCs. Thus, our study demonstrates epigenetic alteration of genomic imprinting during the induction of pluripotency in SSCs and neural differentiation, suggesting that gPS-NSCs can be a useful model to study the roles of imprinted genes in brain development and human neurodevelopmental disorders.
authors.affiliation: a Department of Stem Cell Biology , Konkuk University School of Medicine , Seoul , Korea.|b Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University , Seoul , Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: a Department of Stem Cell Biology , Konkuk University School of Medicine , Seoul , Korea.|b Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University , Seoul , Korea.
authors.forename: Na Young
authors.initials: NY
authors.lastname: Choi
authors.affiliation: a Department of Stem Cell Biology , Konkuk University School of Medicine , Seoul , Korea.|b Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University , Seoul , Korea.
authors.forename: Seung-Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: c Department of Medicine , College of Medicine, Chung-Ang University , Seoul , Korea.
authors.forename: Kisung
authors.initials: K
authors.lastname: Ko
authors.affiliation: d Department of Pathology , Konkuk University Medical Center, Konkuk University School of Medicine , Seoul , Korea.
authors.forename: Tae Sook
authors.initials: TS
authors.lastname: Hwang
authors.affiliation: a Department of Stem Cell Biology , Konkuk University School of Medicine , Seoul , Korea.|b Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University , Seoul , Korea.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Han
authors.affiliation: e Department of Biomedical Science , Hallym University, Chuncheon , Gangwon-do , Korea.
authors.forename: Jisun
authors.initials: J
authors.lastname: Lim
authors.affiliation: f Department of Cell and Developmental Biology , Max Planck Institute for Molecular Biomedicine , Münster , Germany.|g Medical Faculty, University of Münster , Münster , Germany.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: a Department of Stem Cell Biology , Konkuk University School of Medicine , Seoul , Korea.|b Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University , Seoul , Korea.|h Research Institute of Medical Science, Konkuk University , Seoul , Korea.
authors.forename: Kinarm
authors.initials: K
authors.lastname: Ko
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D065150:Cellular Reprogramming / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics; D006801:Humans; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D013093:Spermatogonia / Q000166:cytology / Q000254:growth & development; D013094:Spermatozoa / Q000166:cytology / Q000254:growth & development; D055517:snRNP Core Proteins / Q000235:genetics*
chemical_list: C094335:H19 long non-coding RNA; D011506:Proteins; D062085:RNA, Long Noncoding; C103637:mesoderm specific transcript protein; D055517:snRNP Core Proteins
keywords: Androgenetic imprinting; germline-derived pluripotent stem cells; in vitro model; neural stem cells; spermatogonial stem cells