Chen, Hsu-Hsin, Welling, Maaike, Bloch, Donald B, Muñoz, Javier, Mientjes, Edwin, Chen, Xinjie, Tramp, Cody, Wu, Jie, Yabuuchi, Akiko, Chou, Yu-Fen, Buecker, Christa, Krainer, Adrian, Willemsen, Rob, Heck, Albert J, Geijsen, Niels (October 2014) DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells. Stem Cell Reports, 3 (5). pp. 892-904. ISSN 2213-6711
Abstract
Summary 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.
| Item Type: | Paper |
|---|---|
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > differentiation organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > pluripotency |
| CSHL Authors: | |
| Communities: | CSHL labs > Krainer lab |
| Depositing User: | Matt Covey |
| Date: | 11 October 2014 |
| Date Deposited: | 20 Oct 2014 14:49 |
| Last Modified: | 16 Jul 2021 16:23 |
| PMCID: | PMC4235140 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30847 |
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