Evaluating totipotency using criteria of increasing stringency

Pósfai, Eszter; Schell, John P.; Janiszewski, Adrian; Rovic, Isidora; Murray, Alexander; Bradshaw, Brian; Yamakawa, Tatsuya; Pardon, Tine; Bakkali, Mouna El; Talón, Irene; Geest, Natalie De; Kumar, Pankaj; To, San Kit; Petropoulos, Sophie; Jurisicova, Andrea; Pasque, Vincent; Lanner, Fredrik; Rossant, Janet

doi:10.1038/s41556-020-00609-2

Cited by 123 publications

(121 citation statements)

References 86 publications

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“…However, more recent studies suggest that the purported trophectoderm cells derived from primed hESCs might instead be mis-annotated extraembryonic mesoderm or amnion 6,7 . Furthermore, the purported trophectoderm cells in mouse blastoids generated from extended pluripotent stem cells (EPSCs) instead represent mesoderm-like cells 8 . In light of these conflicting views and the critical need for accurate annotations of cell lineages in embryoids, we reevaluate the two recent papers suggesting that human blastocyst-like structures (or blastoids) can be generated from human pluripotent stem cells or through reprogramming of fibroblasts, respectively 1,2 .…”

Section: Resultsmentioning

confidence: 99%

A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data

Zhao

et al. 2021

Preprint

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Two recent papers in Nature show that human blastocyst-like structures (or blastoids) can be generated from human pluripotent stem cells (Yu et al 2021) or through reprogramming of fibroblasts (Liu et al 2021), respectively. Both papers perform extensive single cell transcriptional analysis and compare blastoid cells with the cells in preimplantation human embryos, leading to a conclusion that the blastoids contain cell lineages corresponding to the epiblast, primitive endoderm and trophectoderm in preimplantation human embryos. Transcriptional analysis is, however, critically dependent on having relevant reference samples, not only of targeted cell types but also of potential alternative cell lineages. For this reason, we have reevaluated the blastoid data with a more comprehensive cellular reference, including extended cultures of blastocysts, several stem cell-based embryo models and a gastrulation stage human specimen. From this reanalysis we resolve that reprogrammed blastoids by Liu et al. fail to generate cells with trophectoderm profiles. Instead, cells identified as trophectoderm lineages in reprogrammed blastoids possess a transcriptional profile more representative of amniotic cells in post-implantation human embryos. Our reanalysis also shows that stem cell-derived blastoids did contain trophectoderm-like cells, highlighting the potential of human blastoids to model blastocyst development.

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Section: Resultsmentioning

confidence: 99%

A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data

Zhao

et al. 2021

Preprint

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“…Similar bipotential chimerism was found with EPSCs, although EPSCs do not have apparent 2C gene expression (Posfai et al, 2021;. However, whether MERVL + 2C-like cells, or EPSCs, or reprogramming intermediates, can develop into complete organisms remains to be found and has spurred significant discussion on the topic (Posfai et al, 2021;Riveiro & Brickman, 2020). Employing an experiment solely from a cultured cell to generate living animals is the most stringent criteria for totipotency and remains elusive.…”

Section: Totipotent Cells 2c-like/mervl+ Cells and Alternative Pomentioning

confidence: 90%

“…Indeed, MERVL+ cells could contribute to embryonic and extraembryonic tissues in chimeras in vivo (Macfarlan et al, 2012). Similar bipotential chimerism was found with EPSCs, although EPSCs do not have apparent 2C gene expression (Posfai et al, 2021;. However, whether MERVL + 2C-like cells, or EPSCs, or reprogramming intermediates, can develop into complete organisms remains to be found and has spurred significant discussion on the topic (Posfai et al, 2021;Riveiro & Brickman, 2020).…”

Section: Totipotent Cells 2c-like/mervl+ Cells and Alternative Pomentioning

confidence: 91%

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Synthetic embryology: Early mammalian embryo modeling systems from cell cultures

Tomoda

Kime

2021

Dev Growth Differ

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Recently, the fields of embryology, developmental biology, stem cell biology, and cell reprogramming, have intersected with synthetic embryo systems (SESs) from cultured cells. Among such SESs, several approaches have engaged early-embryo-like cells, cells with atypical potency, or assembled traditional in vitro stem cell populations with synergy, to advance life discovery systems that may yield emergent knowledge and biotechnical advance. Such models center on the competent generation of blastocyst-like and post-implantation embryo-like forms. Our group, and several others have recently pioneered unique SES strategies covering a broad spectrum of key early embryo-like developmental stages and features to seed an emerging SES field. Herein, we provide a comprehensive perspective of synthetic embryology and the powerful promise that excites us.

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“…While blastoids recapitulated early steps of implantation, in utero culture resulted in malformed structures and/or resorption ( Rivron et al, 2018b ; Kime et al, 2019 ; Li et al, 2019 ; Sozen et al, 2019 ). This could be due to slight variations in gene expression patterns of the involved cells ( Posfai et al, 2021 ). Attempts to improve blastoid formation and post-implantation development are the optimization of TSCs prior to blastoid formation ( Frias-Aldeguer et al, 2019 ) and the targeted modulation of signaling pathways during blastoid formation ( Vrij et al, 2019 ).…”

Section: In Vitro Models Of Mammalian Embryonic Developmentmentioning

confidence: 99%

Development in a Dish—In Vitro Models of Mammalian Embryonic Development

Azhar

Sonnen

2021

Front. Cell Dev. Biol.

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Despite decades of research, the complex processes of embryonic development are not fully understood. The study of mammalian development poses particular challenges such as low numbers of embryos, difficulties in culturing embryos in vitro, and the time to generate mutant lines. With new approaches we can now address questions that had to remain unanswered in the past. One big contribution to studying the molecular mechanisms of development are two- and three-dimensional in vitro model systems derived from pluripotent stem cells. These models, such as blastoids, gastruloids, and organoids, enable high-throughput screens and straightforward gene editing for functional testing without the need to generate mutant model organisms. Furthermore, their use reduces the number of animals needed for research and allows the study of human development. Here, we outline and discuss recent advances in such in vitro model systems to investigate pre-implantation and post-implantation development.

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Evaluating totipotency using criteria of increasing stringency

Cited by 123 publications

References 86 publications

A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data

A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data

Synthetic embryology: Early mammalian embryo modeling systems from cell cultures

Development in a Dish—In Vitro Models of Mammalian Embryonic Development

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