Induction of fetal meiotic oocytes from embryonic stem cells in cynomolgus monkeys

Gyobu‐Motani, Sayuri; Yabuta, Yukihiro; Mizuta, Ken; Katou, Yoshitaka; Okamoto, Ikuhiro; Kawasaki, Masanori; Kitamura, Ayaka; Tsukiyama, Tomoyuki; Iwatani, Chizuru; Tsuchiya, Hideaki; Tsujimura, Taro; Yamamoto, Takuya; Nakamura, Tomonori; Saitou, Mitinori

doi:10.15252/embj.2022112962

Cited by 12 publications

(11 citation statements)

References 72 publications

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“…7b,c ). Xi in F2- AGVT human iPS cells exhibited similar demethylation resistance during both BMP-driven and xrOvary-based hPGCLC differentiation 25 (Fig. 3a and Extended Data Fig.…”

Section: Dna Methylome Reprogrammingmentioning

confidence: 90%

In vitro reconstitution of epigenetic reprogramming in the human germ line

Murase,

Yokogawa,

Yabuta

et al. 2024

Nature

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Epigenetic reprogramming resets parental epigenetic memories and differentiates primordial germ cells (PGCs) into mitotic pro-spermatogonia or oogonia. This process ensures sexually dimorphic germ cell development for totipotency 1 . In vitro reconstitution of epigenetic reprogramming in humans remains a fundamental challenge. Here we establish a strategy for inducing epigenetic reprogramming and differentiation of pluripotent stem-cell-derived human PGC-like cells (hPGCLCs) into mitotic pro-spermatogonia or oogonia, coupled with their extensive amplification (about >10 10 -fold). Bone morphogenetic protein (BMP) signalling is a key driver of these processes. BMP-driven hPGCLC differentiation involves attenuation of the MAPK (ERK) pathway and both de novo and maintenance DNA methyltransferase activities, which probably promote replication-coupled, passive DNA demethylation. hPGCLCs deficient in TET1, an active DNA demethylase abundant in human germ cells 2 , 3 , differentiate into extraembryonic cells, including amnion, with de-repression of key genes that bear bivalent promoters. These cells fail to fully activate genes vital for spermatogenesis and oogenesis, and their promoters remain methylated. Our study provides a framework for epigenetic reprogramming in humans and an important advance in human biology. Through the generation of abundant mitotic pro-spermatogonia and oogonia-like cells, our results also represent a milestone for human in vitro gametogenesis research and its potential translation into reproductive medicine.

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“…7b,c ). Xi in F2- AGVT human iPS cells exhibited similar demethylation resistance during both BMP-driven and xrOvary-based hPGCLC differentiation 25 (Fig. 3a and Extended Data Fig.…”

Section: Dna Methylome Reprogrammingmentioning

confidence: 90%

In vitro reconstitution of epigenetic reprogramming in the human germ line

Murase,

Yokogawa,

Yabuta

et al. 2024

Nature

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“…IVG might also be helpful in saving some endangered animals. Therefore, it is necessary to translate mouse IVG into a scheme suitable for humans and to promote it in NHPs as one of the pre-clinical verifications of the feasibility and safety of IVG [ 106 ].…”

Section: Validating the Safety And Efficacy Of Cellular Therapies Bas...mentioning

confidence: 99%

Current state of stem cell research in non-human primates: an overview

Wu,

Shi,

Yang

et al. 2023

Medical Review

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The remarkable similarity between non-human primates (NHPs) and humans establishes them as essential models for understanding human biology and diseases, as well as for developing novel therapeutic strategies, thereby providing more comprehensive reference data for clinical treatment. Pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells provide unprecedented opportunities for cell therapies against intractable diseases and injuries. As continue to harness the potential of these biotechnological therapies, NHPs are increasingly being employed in preclinical trials, serving as a pivotal tool to evaluate the safety and efficacy of these interventions. Here, we review the recent advancements in the fundamental research of stem cells and the progress made in studies involving NHPs.

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“…Mouse PGCLCs (mPGCLCs) can even give rise to functional mature oocytes or spermatocytes in vitro when aggregated with gonadal somatic cells to generate reconstituted ovaries or testes ( Hayashi et al, 2012 ; Hikabe et al, 2016 ; Ishikura et al, 2016 , 2021 ; Yoshino et al, 2021 ). In addition, human or NHP PGCLCs aggregated with mouse gonadal cells or transplanted into the gonadal niche can further differentiate and give rise to late PGCLCs, pre-meiotic spermatogonia-/oogonia-like cells, or meiotic oocytes ( Yamashiro et al, 2018 ; Hwang et al, 2020 ; Gyobu-Motani et al, 2023 ; Seita et al, 2023 ; Shono et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Generation of marmoset primordial germ cell–like cells under chemically defined conditions

Kurlovich,

Rodriguez Polo,

Dovgusha

et al. 2024

Life Sci. Alliance

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Primordial germ cells (PGCs) are the embryonic precursors of sperm and oocytes, which transmit genetic/epigenetic information across generations. Mouse PGC and subsequent gamete development can be fully reconstituted in vitro, opening up new avenues for germ cell studies in biomedical research. However, PGCs show molecular differences between rodents and humans. Therefore, to establish an in vitro system that is closely related to humans, we studied PGC development in vivo and in vitro in the common marmoset monkeyCallithrix jacchus(cj). Gonadal cjPGCs at embryonic day 74 express SOX17, AP2Ɣ, BLIMP1, NANOG, and OCT4A, which is reminiscent of human PGCs. We established transgene-free induced pluripotent stem cell (cjiPSC) lines from foetal and postnatal fibroblasts. These cjiPSCs, cultured in defined and feeder-free conditions, can be differentiated into precursors of mesendoderm and subsequently into cjPGC-like cells (cjPGCLCs) with a transcriptome similar to human PGCs/PGCLCs. Our results not only pave the way for studying PGC development in a non-human primate in vitro under experimentally controlled conditions, but also provide the opportunity to derive functional marmoset gametes in future studies.

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Induction of fetal meiotic oocytes from embryonic stem cells in cynomolgus monkeys

Cited by 12 publications

References 72 publications

In vitro reconstitution of epigenetic reprogramming in the human germ line

In vitro reconstitution of epigenetic reprogramming in the human germ line

Current state of stem cell research in non-human primates: an overview

Generation of marmoset primordial germ cell–like cells under chemically defined conditions

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