title: Dppa2 and Dppa4 are closely linked SAP motif genes restricted to pluripotent cells and the germ line.
abstract: Despite the enormous medical potential of ESCs, the molecular mechanisms conferring the ability to differentiate into all cell types of the embryo remain elusive. We used an in silico approach to identify genes expressed exclusively in mouse preimplantation embryos and pluripotent cell lines. Two of these genes were developmental pluripotency-associated gene 2 (Dppa2) and Dppa4, which we show are closely linked genes encoding putative nuclear SAP domain proteins expressed in human and mouse pluripotent stem cells and germ cell tumor-derived embryonal carcinoma cells. In the mouse, these genes are transcribed in germinal vesicle-stage oocytes and throughout the cleavage stages of embryogenesis. They then become restricted to the pluripotent inner cell mass of blastocysts and are subsequently downregulated. After gastrulation, Dppa2 and Dppa4 are expressed only in the developing germ line, showing that these genes mark cells of the pluripotent cycle. In the germ line, both genes are downregulated as the germ cells commit to the oogenic pathway or soon after commitment to the spermatogenic pathway. We have observed similar germ line expression profiles for other pluripotent markers, and these results are consistent with the hypothesis that pluripotent markers must be downregulated during fetal germ line development, a process that may be required to facilitate appropriate germ line differentiation. The study of expression and function of pluripotent markers such as Dppa2 and Dppa4 is likely to unveil new aspects of the regulation of pluripotency and germ line development in mammals.
authors.affiliation: Gurdon Institute, Wellcome Trust/Cancer Research United Kingdom, Cambridge, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Maldonado-Saldivia
authors.forename: Jocelyn
authors.initials: J
authors.lastname: van den Bergen
authors.forename: Margarita
authors.initials: M
authors.lastname: Krouskos
authors.forename: Mike
authors.initials: M
authors.lastname: Gilchrist
authors.forename: Caroline
authors.initials: C
authors.lastname: Lee
authors.forename: Ruili
authors.initials: R
authors.lastname: Li
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Sinclair
authors.forename: M Azim
authors.initials: MA
authors.lastname: Surani
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Western
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000502:physiology*; D047108:Embryonic Development; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D009865:Oocytes / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D013737:Testis / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: C519286:Dppa2 protein, mouse; C519287:Dppa4 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D012313:RNA