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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Detalles Bibliográficos
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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/53522
Acceso en línea:http://hdl.handle.net/10230/53522
http://dx.doi.org/10.15252/embj.2021109457
Access Level:acceso abierto
Palabra clave:Cromosoma X
Epigenètica
Cèl·lules germinals
Descripción
Sumario: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.