DAZL limits pluripotency, differentiation, and apoptosis in developing primordial germ cells

Hsu-Hsin Chen, Maaike Welling, Donald B Bloch, Javier Muñoz, Edwin Mientjes, Xinjie Chen, Cody Tramp, Jie Wu, Akiko Yabuuchi, Yu-Fen Chou, Christa Buecker, Adrian Krainer, Rob Willemsen, Albert J Heck, Niels Geijsen

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

The scarcity of primordial germ cells (PGCs) in the developing mammalian embryo hampers robust biochemical analysis of the processes that underlie early germ cell formation. Here, we demonstrate that DAZL, a germ cell-specific RNA binding protein, is a robust PGC marker during in vitro germ cell development. Using Dazl-GFP reporter ESCs, we demonstrate that DAZL plays a central role in a large mRNA/protein interactive network that blocks the translation of core pluripotency factors, including Sox2 and Sall4, as well as of Suz12, a polycomb family member required for differentiation of pluripotent cells. Thus, DAZL limits both pluripotency and somatic differentiation in nascent PGCs. In addition, we observed that DAZL associates with mRNAs of key Caspases and similarly inhibits their translation. This elegant fail-safe mechanism ensures that, whereas loss of DAZL results in prolonged expression of pluripotency factors, teratoma formation is avoided due to the concomitant activation of the apoptotic cascade.

Originele taal-2Engels
Pagina's (van-tot)892-904
Aantal pagina's13
TijdschriftStem Cell Reports
Volume3
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - 11 nov 2014

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