@article{0dd1207462984bb2a419117355ed899c,
title = "Controlled X-chromosome dynamics defines meiotic potential of female mouse in vitro germ cells",
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.",
keywords = "epigenetic reprogramming, in vitro model, meiosis, primordial germ cells, X-chromosome inactivation",
author = "Jacqueline Severino and Moritz Bauer and Tom Mattimoe and Niccol{\`o} Arecco and Luca Cozzuto and Patricia Lorden and Norio Hamada and Yoshiaki Nosaka and Nagaoka, {So I.} and Pauline Audergon and Antonio Tarruell and Holger Heyn and Katsuhiko Hayashi and Mitinori Saitou and Bernhard Payer",
note = "Funding Information: We are grateful to present and previous B.P. lab members for discussions and input. We thank L. Velten for advice on single-cell RNA-seq analysis; F. Nakaki for input on integration of transcription factor vectors and H. Ohta for help in establishing the m220 expansion system. We furthermore acknowledge critical technical support by the CRG core facilities including the CRG Genomics Unit; the CRG/UPF FACS Unit; the Bioinformatics Unit; the Advanced Light Microscopy Unit and the PRBB Animal Facility. 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 Investigaci{\'o}n (AEI) (EUR2019-103817 to B.P.), the AXA Research Fund (to B.P.) and the Agencia de Gestio d{\textquoteright}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{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie grant agreement No 751651. Funding Information: We are grateful to present and previous B.P. lab members for discussions and input. We thank L. Velten for advice on single‐cell RNA‐seq analysis; F. Nakaki for input on integration of transcription factor vectors and H. Ohta for help in establishing the m220 expansion system. We furthermore acknowledge critical technical support by the CRG core facilities including the CRG Genomics Unit; the CRG/UPF FACS Unit; the Bioinformatics Unit; the Advanced Light Microscopy Unit and the PRBB Animal Facility. 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 Investigaci{\'o}n (AEI) (EUR2019‐103817 to B.P.), the AXA Research Fund (to B.P.) and the Agencia de Gestio d{\textquoteright}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{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska‐Curie grant agreement No 751651. Publisher Copyright: {\textcopyright} 2022 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2022",
month = jun,
day = "14",
doi = "10.15252/embj.2021109457",
language = "English",
volume = "41",
pages = "1--23",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "12",
}