title: Over Expression of NANOS3 and DAZL in Human Embryonic Stem Cells.
abstract: The mechanisms underlying human germ cell development are largely unknown, partly due to the scarcity of primordial germ cells and the inaccessibility of the human germline to genetic analysis. Human embryonic stem cells can differentiate to germ cells in vitro and can be genetically modified to study the genetic requirements for germ cell development. Here, we studied NANOS3 and DAZL, which have critical roles in germ cell development in several species, via their over expression in human embryonic stem cells using global transcriptional analysis, in vitro germ cell differentiation, and in vivo germ cell formation assay by xenotransplantation. We found that NANOS3 over expression prolonged pluripotency and delayed differentiation. In addition, we observed a possible connection of NANOS3 with inhibition of apoptosis. For DAZL, our results suggest a post-transcriptional regulation mechanism in hES cells. In addition, we found that DAZL suppressed the translation of OCT4, and affected the transcription of several genes associated with germ cells, cell cycle arrest, and cell migration. Furthermore, DAZL over expressed cells formed spermatogonia-like colonies in a rare instance upon xenotransplantation. These data can be used to further elucidate the role of NANOS3 and DAZL in germ cell development both in vitro and in vivo.
authors: Division of Obstetrics and Gynecology, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Huddinge, SE-141 86, Stockholm, Sweden.
authors: Sarita
authors: S
authors: Panula
authors: Pediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
authors: Ahmed
authors: A
authors: Reda
authors: Pediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
authors: Jan-Bernd
authors: JB
authors: Stukenborg
authors: Department of Genetics and Department of Obstetrics and Gynecology, Institute for Stem Cell Biology and Regenerative Medicine, Center for Reproductive and Stem Cell Biology, Stanford University, Stanford, CA, 94305, United States of America.
authors: Cyril
authors: C
authors: Ramathal
authors: Department of Obstetrics, Gynaecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, PA, 15213, United States of America.
authors: Meena
authors: M
authors: Sukhwani
authors: Pediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, SE-171 76, Stockholm, Sweden.|Sultan Qaboos University, College of Medicine and Health Sciences, Muscat, Oman.
authors: Halima
authors: H
authors: Albalushi
authors: Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
authors: Daniel
authors: D
authors: Edsgärd
authors: Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan.
authors: Michiko
authors: M
authors: Nakamura
authors: Pediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
authors: Olle
authors: O
authors: Söder
authors: Department of Obstetrics, Gynaecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, PA, 15213, United States of America.
authors: Kyle E
authors: KE
authors: Orwig
authors: Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan.|Gladstone Institute of Cardiovascular Disease, San Francisco, CA, 94158, United States of America.
authors: Shinya
authors: S
authors: Yamanaka
authors: Department of Genetics and Department of Obstetrics and Gynecology, Institute for Stem Cell Biology and Regenerative Medicine, Center for Reproductive and Stem Cell Biology, Stanford University, Stanford, CA, 94305, United States of America.|Department of Cell Biology and Neurosciences and Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT, 59717, United States of America.
authors: Renee A
authors: RA
authors: Reijo Pera
authors: Division of Obstetrics and Gynecology, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Huddinge, SE-141 86, Stockholm, Sweden.
authors: Outi
authors: O
authors: Hovatta
mesh_terms: D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005854:Germ Cells / Q000166:cytology; D064593:Heterografts; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C101358:DAZL protein, human; C524848:NANOS3 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins