Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells

Ayumu Suzuki; Masataka Hirasaki; Tomoaki Hishida; Jun Wu; Daiji Okamura; Atsushi Ueda; Masazumi Nishimoto; Yutaka Nakachi; Yosuke Mizuno; Yasushi Okazaki; Yasuhisa Matsui; Juan Carlos Izpisua Belmonte; Akihiko Okuda

doi:10.1038/ncomms11056

Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells

Ayumu Suzuki, Masataka Hirasaki, Tomoaki Hishida, Jun Wu, Daiji Okamura, Atsushi Ueda, Masazumi Nishimoto, Yutaka Nakachi, Yosuke Mizuno, Yasushi Okazaki, Yasuhisa Matsui, Juan Carlos Izpisua Belmonte^*, Akihiko Okuda

^*Corresponding author for this work

Biological, Environmental Sciences and Engineering

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

60 Scopus citations

Abstract

Meiosis is a unique process that allows the generation of reproductive cells. It remains largely unknown how meiosis is initiated in germ cells and why non-germline cells do not undergo meiosis. We previously demonstrated that knockdown of Max expression, a gene encoding a partner of MYC family proteins, strongly activates expression of germ cell-related genes in ESCs. Here we find that complete ablation of Max expression in ESCs results in profound cytological changes reminiscent of cells undergoing meiotic cell division. Furthermore, our analyses uncovers that Max expression is transiently attenuated in germ cells undergoing meiosis in vivo and its forced reduction induces meiosis-like cytological changes in cultured germline stem cells. Mechanistically, Max depletion alterations are, in part, due to impairment of the function of an atypical PRC1 complex (PRC1.6), in which MAX is one of the components. Our data highlight MAX as a new regulator of meiotic onset.

Original language	English (US)
Article number	11056
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11056
State	Published - Mar 30 2016

Bibliographical note

Funding Information:
Acknowledgements We thank Dr Minoru S.H. Ko and Tomoko Okuda for the reporter plasmid bearing the Zscan4 gene promoter and technical assistance, respectively. We are also indebted to Drs Takashi Shinohara, Mitinori Saitou, Hiroyuki Sasaki and Hiroaki Ohishi for their helpful discussions. This study was supported in part by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and primarily by a Grant-in-Aid for the Support Project of Strategic Research at Private Universities to the Saitama Medical University, Research Center for Genomic Medicine. A.O. is the recipient of grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI (grants numbers 25293082, 25670147 and 26112512). A.S. is supported by a grant from JSPS KAKENHI (grant number 26670162). Work in the laboratory of J.C.I.B. was supported by the G. Harold and Leila Y. Mathers Charitable Foundation, Universidad Católica San Antonio de Murcia (UCAM), and The Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002).

ASJC Scopus subject areas

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

Access to Document

10.1038/ncomms11056

Cite this

@article{4e6c833154bb4bfc8542edc9c91b7680,

title = "Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells",

abstract = "Meiosis is a unique process that allows the generation of reproductive cells. It remains largely unknown how meiosis is initiated in germ cells and why non-germline cells do not undergo meiosis. We previously demonstrated that knockdown of Max expression, a gene encoding a partner of MYC family proteins, strongly activates expression of germ cell-related genes in ESCs. Here we find that complete ablation of Max expression in ESCs results in profound cytological changes reminiscent of cells undergoing meiotic cell division. Furthermore, our analyses uncovers that Max expression is transiently attenuated in germ cells undergoing meiosis in vivo and its forced reduction induces meiosis-like cytological changes in cultured germline stem cells. Mechanistically, Max depletion alterations are, in part, due to impairment of the function of an atypical PRC1 complex (PRC1.6), in which MAX is one of the components. Our data highlight MAX as a new regulator of meiotic onset.",

author = "Ayumu Suzuki and Masataka Hirasaki and Tomoaki Hishida and Jun Wu and Daiji Okamura and Atsushi Ueda and Masazumi Nishimoto and Yutaka Nakachi and Yosuke Mizuno and Yasushi Okazaki and Yasuhisa Matsui and Belmonte, {Juan Carlos Izpisua} and Akihiko Okuda",

note = "Funding Information: Acknowledgements We thank Dr Minoru S.H. Ko and Tomoko Okuda for the reporter plasmid bearing the Zscan4 gene promoter and technical assistance, respectively. We are also indebted to Drs Takashi Shinohara, Mitinori Saitou, Hiroyuki Sasaki and Hiroaki Ohishi for their helpful discussions. This study was supported in part by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and primarily by a Grant-in-Aid for the Support Project of Strategic Research at Private Universities to the Saitama Medical University, Research Center for Genomic Medicine. A.O. is the recipient of grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI (grants numbers 25293082, 25670147 and 26112512). A.S. is supported by a grant from JSPS KAKENHI (grant number 26670162). Work in the laboratory of J.C.I.B. was supported by the G. Harold and Leila Y. Mathers Charitable Foundation, Universidad Cat{\'o}lica San Antonio de Murcia (UCAM), and The Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002).",

year = "2016",

month = mar,

day = "30",

doi = "10.1038/ncomms11056",

language = "English (US)",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

TY - JOUR

T1 - Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells

AU - Suzuki, Ayumu

AU - Hirasaki, Masataka

AU - Hishida, Tomoaki

AU - Wu, Jun

AU - Okamura, Daiji

AU - Ueda, Atsushi

AU - Nishimoto, Masazumi

AU - Nakachi, Yutaka

AU - Mizuno, Yosuke

AU - Okazaki, Yasushi

AU - Matsui, Yasuhisa

AU - Belmonte, Juan Carlos Izpisua

AU - Okuda, Akihiko

N1 - Funding Information: Acknowledgements We thank Dr Minoru S.H. Ko and Tomoko Okuda for the reporter plasmid bearing the Zscan4 gene promoter and technical assistance, respectively. We are also indebted to Drs Takashi Shinohara, Mitinori Saitou, Hiroyuki Sasaki and Hiroaki Ohishi for their helpful discussions. This study was supported in part by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and primarily by a Grant-in-Aid for the Support Project of Strategic Research at Private Universities to the Saitama Medical University, Research Center for Genomic Medicine. A.O. is the recipient of grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI (grants numbers 25293082, 25670147 and 26112512). A.S. is supported by a grant from JSPS KAKENHI (grant number 26670162). Work in the laboratory of J.C.I.B. was supported by the G. Harold and Leila Y. Mathers Charitable Foundation, Universidad Católica San Antonio de Murcia (UCAM), and The Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002).

PY - 2016/3/30

Y1 - 2016/3/30

N2 - Meiosis is a unique process that allows the generation of reproductive cells. It remains largely unknown how meiosis is initiated in germ cells and why non-germline cells do not undergo meiosis. We previously demonstrated that knockdown of Max expression, a gene encoding a partner of MYC family proteins, strongly activates expression of germ cell-related genes in ESCs. Here we find that complete ablation of Max expression in ESCs results in profound cytological changes reminiscent of cells undergoing meiotic cell division. Furthermore, our analyses uncovers that Max expression is transiently attenuated in germ cells undergoing meiosis in vivo and its forced reduction induces meiosis-like cytological changes in cultured germline stem cells. Mechanistically, Max depletion alterations are, in part, due to impairment of the function of an atypical PRC1 complex (PRC1.6), in which MAX is one of the components. Our data highlight MAX as a new regulator of meiotic onset.

AB - Meiosis is a unique process that allows the generation of reproductive cells. It remains largely unknown how meiosis is initiated in germ cells and why non-germline cells do not undergo meiosis. We previously demonstrated that knockdown of Max expression, a gene encoding a partner of MYC family proteins, strongly activates expression of germ cell-related genes in ESCs. Here we find that complete ablation of Max expression in ESCs results in profound cytological changes reminiscent of cells undergoing meiotic cell division. Furthermore, our analyses uncovers that Max expression is transiently attenuated in germ cells undergoing meiosis in vivo and its forced reduction induces meiosis-like cytological changes in cultured germline stem cells. Mechanistically, Max depletion alterations are, in part, due to impairment of the function of an atypical PRC1 complex (PRC1.6), in which MAX is one of the components. Our data highlight MAX as a new regulator of meiotic onset.

UR - http://www.scopus.com/inward/record.url?scp=84962424360&partnerID=8YFLogxK

U2 - 10.1038/ncomms11056

DO - 10.1038/ncomms11056

M3 - Article

C2 - 27025988

AN - SCOPUS:84962424360

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11056

ER -

Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this