Generation of Human Oogonia From Induced Pluripotent Stem Cells In Vitro

Yamashiro, Chika; Sasaki, Kotaro; Yabuta, Yukihiro; Nakamura, Tomonori; Okamoto, Ikuhiro; Yokobayashi, Shihori; Murase, Yusuke; Ishikura, Yukiko; Shirane, Kenjiro; Sasaki, Hidetada; Yamamoto, Takuya; Saitou, Mitinori

doi:10.1097/ogx.0000000000000659

Cited by 24 publications

(58 citation statements)

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“…123 These experiments were further refined to eventually remove the need for in-vivo tissue grafting, ultimately providing a platform for complete reconstitution of female gametogenesis from ESCs and iPSCs entirely ex vivo. 124 Parallel studies of human ESCs and iPSCs have provided evidence that, like their murine counterparts, these cells are capable of generating PGC-LCs as well 125,126 and that ovarian follicle-like structures can be formed from human ESCs in culture. 127 Collectively, these studies have prompted widespread, but in our view quite premature, speculation that technologies involving ESCs and iPSCs will one day in the not-too-distant future offer women in need of fertility assistance the opportunity to produce essentially unlimited eggs for assisted reproduction.…”

Section: Reconstitution Of Human Folliculogenesis In Vitromentioning

confidence: 99%

Female Fertility Preservation through Stem Cell-based Ovarian Tissue Reconstitution In Vitro and Ovarian Regeneration In Vivo

Akahori

Woods

Tilly

2019

Clin Med�Insights�Reprod�Health

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Historically, approaches designed to offer women diagnosed with cancer the prospects of having a genetically matched child after completion of their cytotoxic treatments focused on the existing oocyte population as the sole resource available for clinical management of infertility. In this regard, elective oocyte and embryo cryopreservation, as well as autologous ovarian cortical tissue grafting posttreatment, have gained widespread support as options for young girls and reproductive-age women who are faced with cancer to consider. In addition, the use of ovarian protective therapies, including gonadotropin-releasing hormone agonists and sphingosine-1-phosphate analogs, has been put forth as an alternative way to preserve fertility by shielding existing oocytes in the ovaries in vivo from the side-effect damage caused by radiotherapy and many chemotherapeutic regimens. This viewpoint changed with the publication of now numerous reports that adult ovaries of many mammalian species, including humans, contain a rare population of oocyte-producing germ cells—referred to as female germline or oogonial stem cells (OSCs). This new line of study has fueled research into the prospects of generating new oocytes, rather than working with existing oocytes, as a novel approach to sustain or restore fertility in female cancer survivors. Here, we overview the history of work from laboratories around the world focused on improving our understanding of the biology of OSCs and how these cells may be used to reconstitute “artificial” ovarian tissue in vitro or to regenerate damaged ovarian tissue in vivo as future fertility-preservation options.

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Section: Reconstitution Of Human Folliculogenesis In Vitromentioning

confidence: 99%

Female Fertility Preservation through Stem Cell-based Ovarian Tissue Reconstitution In Vitro and Ovarian Regeneration In Vivo

Akahori

Woods

Tilly

2019

Clin Med�Insights�Reprod�Health

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“…The hPGCLC induction system was instrumental in clarifying the mechanism of hPGC specification, which turned out to involve a network and hierarchy of transcription factors that were evolutionarily divergent from those of mPGC specification (Irie et al , 2015; Kojima et al , 2017). More recently, using a culture system involving the aggregation of hPGCLCs with mouse embryonic ovarian somatic cells (xenogeneic rOvaries: xrOvaries), hPGCLCs have been induced into oogonia/gonocyte‐like cells with appropriate epigenetic reprogramming, acquiring a state immediately precursory to entry into the meiotic prophase (Yamashiro et al , 2018). Combined with rapid progress in the analysis of transcriptomes and epigenetic properties of human germ cells at a single‐cell resolution (Gkountela et al , 2015; Guo et al , 2015; Tang et al , 2015; Li et al , 2017), these studies have paved the way to an improved understanding of the mechanism of human germ cell development.…”

Section: Introductionmentioning

confidence: 99%

Long‐term expansion with germline potential of human primordial germ cell‐like cells in vitro

et al. 2020

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Human germ cells perpetuate human genetic and epigenetic information. However, the underlying mechanism remains elusive, due to a lack of appropriate experimental systems. Here, we show that human primordial germ cell-like cells (hPGCLCs) derived from human-induced pluripotent stem cells (hiPSCs) can be propagated to at least~10 6-fold over a period of 4 months under a defined condition in vitro. During expansion, hPGCLCs maintain an early hPGC-like transcriptome and preserve their genome-wide DNA methylation profiles, most likely due to retention of maintenance DNA methyltransferase activity. These characteristics contrast starkly with those of mouse PGCLCs, which, under an analogous condition, show a limited propagation (up to~50-fold) and persist only around 1 week, yet undergo cell-autonomous genome-wide DNA demethylation. Importantly, upon aggregation culture with mouse embryonic ovarian somatic cells in xenogeneic-reconstituted ovaries, expanded hPGCLCs initiate genome-wide DNA demethylation and differentiate into oogonia/gonocyte-like cells, demonstrating their germline potential. By creating a paradigm for hPGCLC expansion, our study uncovers critical divergences in expansion potential and the mechanism for epigenetic reprogramming between the human and mouse germ cell lineage.

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“…For example, in the mouse, many attempts have been performed using the in vitro culture of embryonic gonads and isolated PGCs and more recently in producing gametes from various stem cell types to reproduce meiotic entry and progression (Ge et al, 2015a, Saitou & Miyauchi, 2016). For obvious reasons, this latter approach is particularly useful in humans where promising results have been very recently obtained (Yamashiro et al, 2018). Several studies have reported the successful generation of germ cell-like cells from stem cells, however, until recently convincing evidence that such cells were able to correctly enter meiosis were lacking (Handel et al, 2014, Sun et al, 2014, Tedesco et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Dissecting the initiation of female meiosis in the mouse at single-cell resolution

Wang

Zhang

et al. 2019

Preprint

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ABSTRACTGerm cell meiosis is one of the most finely orchestrated events during gametogenesis with distinct developmental patterns in males and females. However, in mammals, the molecular mechanisms involved in this process remain not well known. Here, we report detailed transcriptome analyses of cell populations present in the mouse female gonadal ridges (E11.5) and the embryonic ovaries from E12.5 to E14.5 using single cell RNA sequencing (scRNA seq). These periods correspond with the initiation and progression of meiosis throughout the first stage of prophase I. We identified 13 transcriptionally distinct cell populations and 7 transcriptionally distinct germ cell subclusters that correspond to mitotic (3 clusters) and meiotic (4 clusters) germ cells. By comparing the signature gene expression pattern of 4 meiotic germ cell clusters, we found that the 4 cell clusters correspond to different cell status en route to meiosis progression, and therefore, our research here characterized detailed transcriptome dynamics during meiotic prophase I. Reconstructing the progression of meiosis along pseudotime, we identified several new genes and molecular pathways with potential critical roles in the mitosis/meiosis transition and early meiotic progression. Last, the heterogeneity within somatic cell populations was also discussed and different cellular states were identified. Our scRNA seq analysis here represents a new important resource for deciphering the molecular pathways driving meiosis initiation and progression in female germ cells and ovarian somatic cells.

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Generation of Human Oogonia From Induced Pluripotent Stem Cells In Vitro

Cited by 24 publications

References 0 publications

Female Fertility Preservation through Stem Cell-based Ovarian Tissue Reconstitution In Vitro and Ovarian Regeneration In Vivo

Female Fertility Preservation through Stem Cell-based Ovarian Tissue Reconstitution In Vitro and Ovarian Regeneration In Vivo

Long‐term expansion with germline potential of human primordial germ cell‐like cells in vitro

Dissecting the initiation of female meiosis in the mouse at single-cell resolution

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