Robust induction of primordial germ cells of white rhinoceros on the brink of extinction

Hayashi, Masafumi; Zywitza, Vera; Naitou, Yuki; Hamazaki, Nobuhiko; Goeritz, Frank; Hermes, Robert; Holtze, Susanne; Lazzari, Giovanna; Cesare, Galli; Stejskal, Jan; Diecke, Sebastian; Hildebrandt, Thomas B.; Hayashi, Kozaburo

doi:10.1126/sciadv.abp9683

Cited by 34 publications

(32 citation statements)

References 52 publications

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“…Thus, wider application for mechanistic studies as well as new avenues in assisted reproduction are anticipated (Cyranoski et al, 2023; Saitou and Hayashi, 2021). Similar technology is already considered for obtaining human germ cells (Hwang et al, 2020; Irie et al, 2015; Sasaki et al ., 2015; Yamashiro et al, 2018), and PGCLCs from endangered species to rescue animals from extinction (Hayashi et al, 2022). Our work provides molecular insights into in vitro oogenesis and identifies critical steps to direct efforts for future improvement.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive comparison of female germ cell developmentin vitroandin vivoidentifies epigenetic gene regulation crucial for oocyte development and embryonic competence

Aizawa

Ozonov

Kawamura

et al. 2023

Preprint

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Germ cells are the origin of new individuals. Hence, specifying germ cell identity is crucial for reproduction. The recent establishment of in vitro culture systems for generating oocytes from mouse pluripotent stem cells provides a basis for progress in studies of oogenesis and reproductive technology. However, currently the developmental competence of in vitro generated oocytes is low compared to in vivo grown oocytes. The causes underlying poor oocyte quality remain to be determined. By reconstituting germ cell development in culture from different developmental starting points within gametogenesis, we show that the differentiation of primordial germ cells (PGCs) and primordial germ cell-like cells (PGCLCs) to growing oocytes (GROs), as well as the subsequent growth of follicles are critical culture steps for specifying competence of fully-grown oocytes (FGOs) for preimplantation development. A systematic comparison of transcriptomes of single oocytes having undergone different in vitro culture trajectories identifies genes normally upregulated during oocyte growth to be susceptible for mis-regulation during in vitro oogenesis. Many of such genes have been described as targets of Polycomb repressive complexes (PRCs). Deregulation of Polycomb repression therefore likely perturbs the accumulation of cytoplasmic factors and/or setting of chromatin states in FGOs that are required for embryonic development after fertilization. Conversely, in vitro derived oocytes often displayed failure of zygotic genome activation (ZGA) and abnormal acquisition of 5-hydroxymethylcytosine (5hmC) on maternal chromosomes after activation. In addition, subcellular delocalization of pyruvate dehydrogenase (PDH) and of STELLA were observed suggesting new molecular markers for defective oocyte development. Our study identifies epigenetic regulation at an early stage of oogenesis as crucial for developmental competence and suggests specific in vitro culture steps as targets for improving oocyte quality.

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Section: Discussionmentioning

confidence: 99%

Comprehensive comparison of female germ cell developmentin vitroandin vivoidentifies epigenetic gene regulation crucial for oocyte development and embryonic competence

Aizawa

Ozonov

Kawamura

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Thus, wider application for mechanistic studies as well as new avenues in assisted reproduction is anticipated (Saitou & Hayashi, 2021; Cyranoski et al , 2023). Similar technology is already considered for obtaining human germ cells (Irie et al , 2015; Sasaki et al , 2015; Yamashiro et al , 2018; Hwang et al , 2020), and PGCLCs from endangered species to rescue animals from extinction (Hayashi et al , 2022). Our work provides molecular insights into in vitro oogenesis and identifies critical steps to direct efforts for future improvement.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic regulation limits competence of pluripotent stem cell‐derived oocytes

Aizawa,

Ozonov,

Kawamura

et al. 2023

The EMBO Journal

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Recent studies have reported the differentiation of pluripotent cells into oocytes in vitro. However, the developmental competence of in vitro‐generated oocytes remains low. Here, we perform a comprehensive comparison of mouse germ cell development in vitro over all culture steps versus in vivo with the goal to understand mechanisms underlying poor oocyte quality. We show that the in vitro differentiation of primordial germ cells to growing oocytes and subsequent follicle growth is critical for competence for preimplantation development. Systematic transcriptome analysis of single oocytes that were subjected to different culture steps identifies genes that are normally upregulated during oocyte growth to be susceptible for misregulation during in vitro oogenesis. Many misregulated genes are Polycomb targets. Deregulation of Polycomb repression is therefore a key cause and the earliest defect known in in vitro oocyte differentiation. Conversely, structurally normal in vitro‐derived oocytes fail at zygotic genome activation and show abnormal acquisition of 5‐hydroxymethylcytosine on maternal chromosomes. Our data identify epigenetic regulation at an early stage of oogenesis limiting developmental competence and suggest opportunities for future improvements.

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“…Third, PSCs could be potentially used for endangered species restoration through differentiation into gametes. Such a strategy is in development for the white rhinoceros [ 11 ]. This review focuses on the technical aspects of ES and iPS cell derivation and may be useful for planning experiments on PSC derivation from novel species.…”

Section: Advantages Of Carnivora Pluripotent Stem Cellsmentioning

confidence: 99%

Pluripotent Stem Cells of Order Carnivora: Technical Perspective

Мензоров

2023

IJMS

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Human and mouse induced pluripotent stem cells (PSCs) are widely used for studying early embryonic development and for modeling of human diseases. Derivation and studying of PSCs from model organisms beyond commonly used mice and rats may provide new insights into the modeling and treating human diseases. The order Carnivora representatives possess unique features and are already used for modeling human-related traits. This review focuses on the technical aspects of derivation of the Carnivora species PSCs as well as their characterization. Current data on dog, feline, ferret, and American mink PSCs are summarized.

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Robust induction of primordial germ cells of white rhinoceros on the brink of extinction

Cited by 34 publications

References 52 publications

Comprehensive comparison of female germ cell developmentin vitroandin vivoidentifies epigenetic gene regulation crucial for oocyte development and embryonic competence

Comprehensive comparison of female germ cell developmentin vitroandin vivoidentifies epigenetic gene regulation crucial for oocyte development and embryonic competence

Epigenetic regulation limits competence of pluripotent stem cell‐derived oocytes

Pluripotent Stem Cells of Order Carnivora: Technical Perspective

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