DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells

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 (2014) DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells. Stem Cell Reports, 3 (5). pp. 892-904. ISSN 2213-6711

URL: http://www.ncbi.nlm.nih.gov/pubmed/25418731
DOI: 10.1016/j.stemcr.2014.09.003

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 Deposited: 20 Oct 2014 14:49
Last Modified: 26 Nov 2014 19:59
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30847

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