title: Divergent RNA-binding proteins, DAZL and VASA, induce meiotic progression in human germ cells derived in vitro.
abstract: Our understanding of human germ cell development is limited in large part due to inaccessibility of early human development to molecular genetic analysis. Pluripotent human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been shown to differentiate to cells of all three embryonic germ layers, as well as germ cells in vitro, and thus may provide a model for the study of the genetics and epigenetics of human germline. Here, we examined whether intrinsic germ cell translational, rather than transcriptional, factors might drive germline formation and/or differentiation from human pluripotent stem cells in vitro. We observed that, with overexpression of VASA (DDX4) and/or DAZL (Deleted in Azoospermia Like), both hESCs and iPSCs differentiated to primordial germ cells, and maturation and progression through meiosis was enhanced. These results demonstrate that evolutionarily unrelated and divergent RNA-binding proteins can promote meiotic progression of human-derived germ cells in vitro. These studies describe an in vitro model for exploring specifics of human meiosis, a process that is remarkably susceptible to errors that lead to different infertility-related diseases.
authors.affiliation: Institute for Stem Cell Biology & Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford University, Palo Alto, CA, USA.
authors.forename: Jose V
authors.initials: JV
authors.lastname: Medrano
authors.forename: Cyril
authors.initials: C
authors.lastname: Ramathal
authors.forename: Ha N
authors.initials: HN
authors.lastname: Nguyen
authors.forename: Carlos
authors.initials: C
authors.lastname: Simon
authors.forename: Renee A
authors.initials: RA
authors.lastname: Reijo Pera
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D053487:DEAD-box RNA Helicases / Q000378:metabolism / Q000502:physiology*; D019175:DNA Methylation; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008540:Meiosis; D051379:Mice; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000502:physiology; D017422:Sequence Analysis, DNA; D013573:Synaptonemal Complex / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; C101358:DAZL protein, human; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C498288:DDX4 protein, human; D053487:DEAD-box RNA Helicases