An RNA-interacting protein network regulates pluripotency in mammalian primordial germ cells (in vitro, in vivo)

ABSTRACT: Primordial germ cells (PGCs) are the embryonic precursors to egg and sperm. When removed from the embryonic gonad, PGCs can give rise to embryonic germ cell lines (EGs), pluripotent stem cells that display most of the characteristics of embryonic stem cells (ESCs) including the ability to form teratomas and to contribute to chimera formation. In mice, EG cells can be derived between E8.5 up to E12.5 of embryonic development, at which point the PGCs undergo sexual differentiation and in the male transition into unipotent gonocytes. Dazl, a germ cell-specific RNA-binding protein, is specifically expressed in developing PGCs and is required for proper germ cell development. Dazl knockout mice are infertile, but the molecular mechanisms underlying this phenotype are still unknown. Here we demonstrate that Dazl localizes in granular structures in mammalian PGCs but not in ESCs. We demonstrate Dazl plays a central role in a large mRNA/protein interactive network that includes members of Fragile-X family RNA-binding proteins. We demonstrate that Dazl and Fxr1 play a central role in these granules and directly regulate the translation of specific core pluripotency factors, including Sox2 and Suz12. Global gene expression changes during in vitro germ cell differentiation from murine ES cells and comparison to in vivo germ cells. In vitro primordial germ cells differentiated from Stella-GFP ES cells and Dazl-GFP ES cells. The GFP-positive cells were isolated by FACS analysis. Dazl-GFP+ cells were isolated from transgenic E13.5 embryonic gonads and P7-P11 juvenile mouse testes. The global gene expression profiles were analyzed by Agilent Mouse Whole Genome 4X44K one-color microarrays. Two replicates per condition.

ORGANISM(S): Mus musculus

SUBMITTER: Niels Geijsen 

PROVIDER: E-GEOD-39546 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress