Regulation of mammalian totipotency: a molecular perspective from in vivo and in vitro studies

Nakatani, Tsunetoshi; Torres-Padilla, Maria-Elena

doi:10.1016/j.gde.2023.102083

Cited by 5 publications

(2 citation statements)

References 57 publications

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“…Recently, it was reported that MERVL promotes totipotency-to-pluripotency transition by repressing 2C genes through an unknown mechanism (Sakashita et al, 2023). This is an intriguing discovery given that MERVL is positively associated with 2C gene expression in 2-cell embryos, 2C-like cells, and totipotent-like cells (Nakatani and Torres-Padilla, 2023). In current study, de-repression of 2C genes was not observed despite that MERVL was strongly downregulated (>35-fold) upon MT2_Mmi ( Fig.…”

Section: Discussionmentioning

confidence: 97%

Systematic Perturbation of Thousands of Retroviral LTRs in Mouse Embryos

Yang,

Cook,

Chen

2023

Preprint

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In mammals, many retrotransposons are de-repressed during zygotic genome activation (ZGA). However, their functions in early development remain elusive largely due to the challenge to simultaneously manipulate thousands of retrotransposon insertions in embryos. Here, we employed epigenome editing to perturb the long terminal repeat (LTR) MT2_Mm, a well-known ZGA and totipotency marker that exists in ~2667 insertions throughout the mouse genome. CRISPRi robustly repressed 2485 (~93%) MT2_Mm insertions and 1090 (~55%) insertions of the closely related MT2C_Mm in 2-cell embryos. Remarkably, such perturbation caused down-regulation of hundreds of ZGA genes at the 2-cell stage and embryonic arrest mostly at the morula stage. Mechanistically, MT2_Mm/MT2C_Mm primarily served as alternative ZGA promoters activated by OBOX proteins. Thus, through unprecedented large-scale epigenome editing, we addressed to what extent MT2_Mm/MT2C_Mm regulates ZGA and preimplantation development. Our approach could be adapted to systematically perturb retrotransposons in other mammalian embryos as it does not require transgenic animals.

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Section: Discussionmentioning

confidence: 97%

Systematic Perturbation of Thousands of Retroviral LTRs in Mouse Embryos

Yang,

Cook,

Chen

2023

Preprint

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“…As recent research on stem cell-derived embryoids has impressively demonstrated, a great variety of constructs of differing complexity and completeness can be produced when using various advanced in vitro technologies [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. It does not appear trivial anymore to define a border line between stem cell-derived embryoids and organoids.…”

Section: A Recent Discussion About Ethical Guidelines and The Term "E...mentioning

confidence: 99%

Stem Cell-Derived Organoids, Embryoids, and Embryos: Advances in Organismic Development In Vitro Force Us to Re-Focus on Ethical and Legal Aspects of Model Choice

Denker

2023

Organoids

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While research on stem cell-derived tissues and organoids is rapidly expanding, the technically related creation of complex embryoids has recently excited a vivid discussion since it raises ethical questions about individuation and the possible gain of viability. The present study focuses on the onset of organismic development and the proposed biological and legal definitions for the terms embryo, embryoid, and organoid. It is concluded that such considerations have become important for investigators’ choices of the appropriate in vitro model systems, allowing the formation of organoids vs. complex embryoids.

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Unlocking trophectoderm mysteries: In vivo and in vitro perspectives on human and mouse trophoblast fate induction

Azagury,

Buganim

2024

Developmental Cell

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Regulation of mammalian totipotency: a molecular perspective from in vivo and in vitro studies

Cited by 5 publications

References 57 publications

Systematic Perturbation of Thousands of Retroviral LTRs in Mouse Embryos

Systematic Perturbation of Thousands of Retroviral LTRs in Mouse Embryos

Stem Cell-Derived Organoids, Embryoids, and Embryos: Advances in Organismic Development In Vitro Force Us to Re-Focus on Ethical and Legal Aspects of Model Choice

Unlocking trophectoderm mysteries: In vivo and in vitro perspectives on human and mouse trophoblast fate induction

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