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

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

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

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dc.contributor.author Severino, Jacqueline, 1990-
dc.contributor.author Bauer, Moritz, 1987-
dc.contributor.author Mattimoe, Tom
dc.contributor.author Arecco, Niccolò
dc.contributor.author Cozzuto, Luca
dc.contributor.author Lorden, Patricia
dc.contributor.author Hamada, Norio
dc.contributor.author Nosaka, Yoshiaki
dc.contributor.author Nagaoka, So I.
dc.contributor.author Audergon, Pauline
dc.contributor.author Tarruell Pellegrin, Antonio,1990-
dc.contributor.author Heyn, Holger
dc.contributor.author Hayashi, Katsuhiko
dc.contributor.author Saitou, Mitinori
dc.contributor.author Payer, Bernhard
dc.date.accessioned 2022-06-17T10:31:58Z
dc.date.available 2022-06-17T10:31:58Z
dc.date.issued 2022
dc.description.abstract 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.
dc.description.sponsorship 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 751651
dc.format.mimetype application/pdf
dc.identifier.citation Severino J, Bauer M, Mattimoe T, Arecco N, Cozzuto L, Lorden P. Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells. EMBO J. 2022 Jun 14;41(12):e109457. DOI:10.15252/embj.2021109457
dc.identifier.doi http://dx.doi.org/10.15252/embj.2021109457
dc.identifier.issn 0261-4189
dc.identifier.uri http://hdl.handle.net/10230/53522
dc.language.iso eng
dc.publisher EMBO Press
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/751651
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55275-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Cromosoma X
dc.subject.other Epigenètica
dc.subject.other Cèl·lules germinals
dc.title Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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