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

doi:10.1016/j.stemcr.2014.09.003

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

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

68 Citaten (Scopus)

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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-2	Engels
Pagina's (van-tot)	892-904
Aantal pagina's	13
Tijdschrift	Stem Cell Reports
Volume	3
Nummer van het tijdschrift	5
DOI's	https://doi.org/10.1016/j.stemcr.2014.09.003
Status	Gepubliceerd - 11 nov. 2014

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10.1016/j.stemcr.2014.09.003Licentie: CC BY-NC-ND

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Chen, H.-H., Welling, M., Bloch, D. B., Muñoz, J., Mientjes, E., Chen, X., Tramp, C., Wu, J., Yabuuchi, A., Chou, Y.-F., Buecker, C., Krainer, A., Willemsen, R., Heck, A. J., & Geijsen, N. (2014). DAZL limits pluripotency, differentiation, and apoptosis in developing primordial germ cells. Stem Cell Reports, 3(5), 892-904. https://doi.org/10.1016/j.stemcr.2014.09.003

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

abstract = "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.",

author = "Hsu-Hsin Chen and Maaike Welling and Bloch, {Donald B} and Javier Mu{\~n}oz and Edwin Mientjes and Xinjie Chen and Cody Tramp and Jie Wu and Akiko Yabuuchi and Yu-Fen Chou and Christa Buecker and Adrian Krainer and Rob Willemsen and Heck, {Albert J} and Niels Geijsen",

year = "2014",

month = nov,

day = "11",

doi = "10.1016/j.stemcr.2014.09.003",

language = "English",

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journal = "Stem Cell Reports",

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T1 - DAZL limits pluripotency, differentiation, and apoptosis in developing primordial germ cells

AU - Chen, Hsu-Hsin

AU - Welling, Maaike

AU - Bloch, Donald B

AU - Muñoz, Javier

AU - Mientjes, Edwin

AU - Chen, Xinjie

AU - Tramp, Cody

AU - Wu, Jie

AU - Yabuuchi, Akiko

AU - Chou, Yu-Fen

AU - Buecker, Christa

AU - Krainer, Adrian

AU - Willemsen, Rob

AU - Heck, Albert J

AU - Geijsen, Niels

PY - 2014/11/11

Y1 - 2014/11/11

N2 - 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.

AB - 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.

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DO - 10.1016/j.stemcr.2014.09.003

M3 - Article

C2 - 25418731

SN - 2213-6711

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EP - 904

JO - Stem Cell Reports

JF - Stem Cell Reports

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ER -

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

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