PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not naïve ESCs

Yongli Shan; Zechuan Liang; Qi Xing; Tian Zhang; Bo Wang; Shulan Tian; Wenhao Huang; Yanqi Zhang; Jiao Yao; Yanling Zhu; Ke Huang; Yujian Liu; Xiaoshan Wang; Qianyu Chen; Jian Zhang; Bizhi Shang; Shengbiao Li; Xi Shi; Baojian Liao; Cong Zhang; Keyu Lai; Xiaofen Zhong; Xiaodong Shu; Jinyong Wang; Hongjie Yao; Jiekai Chen; Duanqing Pei; Guangjin Pan

doi:10.1038/s41467-017-00668-4

PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not naïve ESCs

Yongli Shan, Zechuan Liang, Qi Xing, Tian Zhang, Bo Wang, Shulan Tian, Wenhao Huang, Yanqi Zhang, Jiao Yao, Yanling Zhu, Ke Huang, Yujian Liu, Xiaoshan Wang, Qianyu Chen, Jian Zhang, Bizhi Shang, Shengbiao Li, Xi Shi, Baojian Liao, Cong ZhangKeyu Lai, Xiaofen Zhong, Xiaodong Shu, Jinyong Wang, Hongjie Yao, Jiekai Chen, Duanqing Pei, Guangjin Pan

Quantitative Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Polycomb repressive complex 2 and the epigenetic mark that it deposits, H3K27me3, are evolutionarily conserved and play critical roles in development and cancer. However, their roles in cell fate decisions in early embryonic development remain poorly understood. Here we report that knockout of polycomb repressive complex 2 genes in human embryonic stem cells causes pluripotency loss and spontaneous differentiation toward a meso-endoderm fate, owing to de-repression of BMP signalling. Moreover, human embryonic stem cells with deletion of EZH1 or EZH2 fail to differentiate into ectoderm lineages. We further show that polycomb repressive complex 2-deficient mouse embryonic stem cells also release Bmp4 but retain their pluripotency. However, when converted into a primed state, they undergo spontaneous differentiation similar to that of hESCs. In contrast, polycomb repressive complex 2 is dispensable for pluripotency when human embryonic stem cells are converted into the naive state. Our studies reveal both lineage- and pluripotent state-specific roles of polycomb repressive complex 2 in cell fate decisions.

Original language	English (US)
Article number	672
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00668-4
State	Published - Dec 1 2017

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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10.1038/s41467-017-00668-4

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Shan, Y., Liang, Z., Xing, Q., Zhang, T., Wang, B., Tian, S., Huang, W., Zhang, Y., Yao, J., Zhu, Y., Huang, K., Liu, Y., Wang, X., Chen, Q., Zhang, J., Shang, B., Li, S., Shi, X., Liao, B., ... Pan, G. (2017). PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not naïve ESCs. Nature communications, 8(1), Article 672. https://doi.org/10.1038/s41467-017-00668-4

Shan, Y, Liang, Z, Xing, Q, Zhang, T, Wang, B, Tian, S, Huang, W, Zhang, Y, Yao, J, Zhu, Y, Huang, K, Liu, Y, Wang, X, Chen, Q, Zhang, J, Shang, B, Li, S, Shi, X, Liao, B, Zhang, C, Lai, K, Zhong, X, Shu, X, Wang, J, Yao, H, Chen, J, Pei, D & Pan, G 2017, 'PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not naïve ESCs', Nature communications, vol. 8, no. 1, 672. https://doi.org/10.1038/s41467-017-00668-4

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title = "PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not na{\"i}ve ESCs",

abstract = "Polycomb repressive complex 2 and the epigenetic mark that it deposits, H3K27me3, are evolutionarily conserved and play critical roles in development and cancer. However, their roles in cell fate decisions in early embryonic development remain poorly understood. Here we report that knockout of polycomb repressive complex 2 genes in human embryonic stem cells causes pluripotency loss and spontaneous differentiation toward a meso-endoderm fate, owing to de-repression of BMP signalling. Moreover, human embryonic stem cells with deletion of EZH1 or EZH2 fail to differentiate into ectoderm lineages. We further show that polycomb repressive complex 2-deficient mouse embryonic stem cells also release Bmp4 but retain their pluripotency. However, when converted into a primed state, they undergo spontaneous differentiation similar to that of hESCs. In contrast, polycomb repressive complex 2 is dispensable for pluripotency when human embryonic stem cells are converted into the naive state. Our studies reveal both lineage- and pluripotent state-specific roles of polycomb repressive complex 2 in cell fate decisions.",

author = "Yongli Shan and Zechuan Liang and Qi Xing and Tian Zhang and Bo Wang and Shulan Tian and Wenhao Huang and Yanqi Zhang and Jiao Yao and Yanling Zhu and Ke Huang and Yujian Liu and Xiaoshan Wang and Qianyu Chen and Jian Zhang and Bizhi Shang and Shengbiao Li and Xi Shi and Baojian Liao and Cong Zhang and Keyu Lai and Xiaofen Zhong and Xiaodong Shu and Jinyong Wang and Hongjie Yao and Jiekai Chen and Duanqing Pei and Guangjin Pan",

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AU - Shan, Yongli

AU - Liang, Zechuan

AU - Xing, Qi

AU - Zhang, Tian

AU - Wang, Bo

AU - Tian, Shulan

AU - Huang, Wenhao

AU - Zhang, Yanqi

AU - Yao, Jiao

AU - Zhu, Yanling

AU - Huang, Ke

AU - Liu, Yujian

AU - Wang, Xiaoshan

AU - Chen, Qianyu

AU - Zhang, Jian

AU - Shang, Bizhi

AU - Li, Shengbiao

AU - Shi, Xi

AU - Liao, Baojian

AU - Zhang, Cong

AU - Lai, Keyu

AU - Zhong, Xiaofen

AU - Shu, Xiaodong

AU - Wang, Jinyong

AU - Yao, Hongjie

AU - Chen, Jiekai

AU - Pei, Duanqing

AU - Pan, Guangjin

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Polycomb repressive complex 2 and the epigenetic mark that it deposits, H3K27me3, are evolutionarily conserved and play critical roles in development and cancer. However, their roles in cell fate decisions in early embryonic development remain poorly understood. Here we report that knockout of polycomb repressive complex 2 genes in human embryonic stem cells causes pluripotency loss and spontaneous differentiation toward a meso-endoderm fate, owing to de-repression of BMP signalling. Moreover, human embryonic stem cells with deletion of EZH1 or EZH2 fail to differentiate into ectoderm lineages. We further show that polycomb repressive complex 2-deficient mouse embryonic stem cells also release Bmp4 but retain their pluripotency. However, when converted into a primed state, they undergo spontaneous differentiation similar to that of hESCs. In contrast, polycomb repressive complex 2 is dispensable for pluripotency when human embryonic stem cells are converted into the naive state. Our studies reveal both lineage- and pluripotent state-specific roles of polycomb repressive complex 2 in cell fate decisions.

AB - Polycomb repressive complex 2 and the epigenetic mark that it deposits, H3K27me3, are evolutionarily conserved and play critical roles in development and cancer. However, their roles in cell fate decisions in early embryonic development remain poorly understood. Here we report that knockout of polycomb repressive complex 2 genes in human embryonic stem cells causes pluripotency loss and spontaneous differentiation toward a meso-endoderm fate, owing to de-repression of BMP signalling. Moreover, human embryonic stem cells with deletion of EZH1 or EZH2 fail to differentiate into ectoderm lineages. We further show that polycomb repressive complex 2-deficient mouse embryonic stem cells also release Bmp4 but retain their pluripotency. However, when converted into a primed state, they undergo spontaneous differentiation similar to that of hESCs. In contrast, polycomb repressive complex 2 is dispensable for pluripotency when human embryonic stem cells are converted into the naive state. Our studies reveal both lineage- and pluripotent state-specific roles of polycomb repressive complex 2 in cell fate decisions.

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PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not naïve ESCs

Abstract

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