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DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells
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 dev...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235140/ https://www.ncbi.nlm.nih.gov/pubmed/25418731 http://dx.doi.org/10.1016/j.stemcr.2014.09.003 |
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author | 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 |
author_facet | 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 |
author_sort | Chen, Hsu-Hsin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4235140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-42351402014-11-19 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 Stem Cell Reports Resource 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. Elsevier 2014-10-11 /pmc/articles/PMC4235140/ /pubmed/25418731 http://dx.doi.org/10.1016/j.stemcr.2014.09.003 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Resource 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 DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells |
title | DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells |
title_full | DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells |
title_fullStr | DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells |
title_full_unstemmed | DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells |
title_short | DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells |
title_sort | dazl limits pluripotency, differentiation, and apoptosis in developing primordial germ cells |
topic | Resource |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235140/ https://www.ncbi.nlm.nih.gov/pubmed/25418731 http://dx.doi.org/10.1016/j.stemcr.2014.09.003 |
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