Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells

The mammalian germline is characterized by extensive epigenetic reprogramming during its development into functional eggs and sperm. Specifically, the epigenome requires resetting before parental marks can be established and transmitted to the next generation. In the female germline, X-chromosome in...

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Autores: Severino, Jacqueline, 1990-, Bauer, Moritz, 1987-, Mattimoe, Tom, Arecco, Niccolò, Cozzuto, Luca, Lorden, Patricia, Hamada, Norio, Nosaka, Yoshiaki, Nagaoka, So I., Audergon, Pauline, Tarruell Pellegrin, Antonio,1990-, Heyn, Holger, Hayashi, Katsuhiko, Saitou, Mitinori, Payer, Bernhard
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/53522
Acesso em linha:http://hdl.handle.net/10230/53522
http://dx.doi.org/10.15252/embj.2021109457
Access Level:acceso abierto
Palavra-chave:Cromosoma X
Epigenètica
Cèl·lules germinals
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spelling Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cellsSeverino, Jacqueline, 1990-Bauer, Moritz, 1987-Mattimoe, TomArecco, NiccolòCozzuto, LucaLorden, PatriciaHamada, NorioNosaka, YoshiakiNagaoka, So I.Audergon, PaulineTarruell Pellegrin, Antonio,1990-Heyn, HolgerHayashi, KatsuhikoSaitou, MitinoriPayer, BernhardCromosoma XEpigenèticaCèl·lules germinalsThe mammalian germline is characterized by extensive epigenetic reprogramming during its development into functional eggs and sperm. Specifically, the epigenome requires resetting before parental marks can be established and transmitted to the next generation. In the female germline, X-chromosome inactivation and reactivation are among the most prominent epigenetic reprogramming events, yet very little is known about their kinetics and biological function. Here, we investigate X-inactivation and reactivation dynamics using a tailor-made in vitro system of primordial germ cell-like cell (PGCLC) differentiation from mouse embryonic stem cells. We find that X-inactivation in PGCLCs in vitro and in germ cell-competent epiblast cells in vivo is moderate compared to somatic cells, and frequently characterized by escaping genes. X-inactivation is followed by step-wise X-reactivation, which is mostly completed during meiotic prophase I. Furthermore, we find that PGCLCs which fail to undergo X-inactivation or reactivate too rapidly display impaired meiotic potential. Thus, our data reveal fine-tuned X-chromosome remodelling as a critical feature of female germ cell development towards meiosis and oogenesis.This work was supported by the Spanish Ministry of Science, Innovation and Universities (BFU2014-55275-P, BFU2017-88407-P to B.P.), the Agencia Estatal de Investigación (AEI) (EUR2019-103817 to B.P.), the AXA Research Fund (to B.P.) and the Agencia de Gestio d’Ajuts Universitaris i de Recerca (AGAUR, 2017 SGR 346 to B.P.). We would like to thank the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership and to the “Centro de Excelencia Severo Ochoa.” We also acknowledge support of the CERCA Programme of the Generalitat de Catalunya. N.A. is supported by an EMBO postdoctoral fellowship (LTF 695-2019). J.S. and M.B. were supported by La Caixa International PhD Fellowships and J.S. by a travel grant from the Company of Biologists (Development Journal). P.A. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 751651EMBO Press202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/53522http://dx.doi.org/10.15252/embj.2021109457reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésinfo:eu-repo/grantAgreement/EC/H2020/751651info:eu-repo/grantAgreement/ES/1PE/BFU2014-55275-Pinfo:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P© 2022 Jacqueline Severino et al. Published under the terms of the CC BY 4.0 licensehttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/535222026-06-12T07:21:37Z
dc.title.none.fl_str_mv Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells
title Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells
spellingShingle Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells
Severino, Jacqueline, 1990-
Cromosoma X
Epigenètica
Cèl·lules germinals
title_short Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells
title_full Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells
title_fullStr Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells
title_full_unstemmed Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells
title_sort Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells
dc.creator.none.fl_str_mv Severino, Jacqueline, 1990-
Bauer, Moritz, 1987-
Mattimoe, Tom
Arecco, Niccolò
Cozzuto, Luca
Lorden, Patricia
Hamada, Norio
Nosaka, Yoshiaki
Nagaoka, So I.
Audergon, Pauline
Tarruell Pellegrin, Antonio,1990-
Heyn, Holger
Hayashi, Katsuhiko
Saitou, Mitinori
Payer, Bernhard
author Severino, Jacqueline, 1990-
author_facet Severino, Jacqueline, 1990-
Bauer, Moritz, 1987-
Mattimoe, Tom
Arecco, Niccolò
Cozzuto, Luca
Lorden, Patricia
Hamada, Norio
Nosaka, Yoshiaki
Nagaoka, So I.
Audergon, Pauline
Tarruell Pellegrin, Antonio,1990-
Heyn, Holger
Hayashi, Katsuhiko
Saitou, Mitinori
Payer, Bernhard
author_role author
author2 Bauer, Moritz, 1987-
Mattimoe, Tom
Arecco, Niccolò
Cozzuto, Luca
Lorden, Patricia
Hamada, Norio
Nosaka, Yoshiaki
Nagaoka, So I.
Audergon, Pauline
Tarruell Pellegrin, Antonio,1990-
Heyn, Holger
Hayashi, Katsuhiko
Saitou, Mitinori
Payer, Bernhard
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cromosoma X
Epigenètica
Cèl·lules germinals
topic Cromosoma X
Epigenètica
Cèl·lules germinals
description The mammalian germline is characterized by extensive epigenetic reprogramming during its development into functional eggs and sperm. Specifically, the epigenome requires resetting before parental marks can be established and transmitted to the next generation. In the female germline, X-chromosome inactivation and reactivation are among the most prominent epigenetic reprogramming events, yet very little is known about their kinetics and biological function. Here, we investigate X-inactivation and reactivation dynamics using a tailor-made in vitro system of primordial germ cell-like cell (PGCLC) differentiation from mouse embryonic stem cells. We find that X-inactivation in PGCLCs in vitro and in germ cell-competent epiblast cells in vivo is moderate compared to somatic cells, and frequently characterized by escaping genes. X-inactivation is followed by step-wise X-reactivation, which is mostly completed during meiotic prophase I. Furthermore, we find that PGCLCs which fail to undergo X-inactivation or reactivate too rapidly display impaired meiotic potential. Thus, our data reveal fine-tuned X-chromosome remodelling as a critical feature of female germ cell development towards meiosis and oogenesis.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/53522
http://dx.doi.org/10.15252/embj.2021109457
url http://hdl.handle.net/10230/53522
http://dx.doi.org/10.15252/embj.2021109457
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/EC/H2020/751651
info:eu-repo/grantAgreement/ES/1PE/BFU2014-55275-P
info:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P
dc.rights.none.fl_str_mv © 2022 Jacqueline Severino et al. Published under the terms of the CC BY 4.0 license
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © 2022 Jacqueline Severino et al. Published under the terms of the CC BY 4.0 license
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv EMBO Press
publisher.none.fl_str_mv EMBO Press
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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