Divergent RNA‐binding Proteins, DAZL and VASA, Induce Meiotic Progression in Human Germ Cells Derived in Vitro123. (14th February 2012)

• Record Type: Journal Article
• Authors: Medrano, Jose V.; Ramathal, Cyril; Nguyen, Ha N.; Simon, Carlos; Reijo Pera, Renee A.
• Is Part Of: Stem cells. Volume 30:Number 3(2012)
• Page Start: 441
• Page End: 451
• Publication Date: 2012-02-14
• Subjects: DAZL -- VASA -- Meiosis -- Induced pluripotent stem cells -- Human embryonic stem cells; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1012
• Languages: English
• ISSNs: 1066-5099

Abstract

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. STEM CELLS 2012;30:441–451