Capture of mouse and human stem cells with features of formative pluripotency

Kinoshita, Masaki; Barber, M.; Mansfield, William; Cui, Yingzhi; Spindlow, Daniel; Stirparo, Giuliano Giuseppe; Dietmann, Sabine; Nichols, Jennifer; Smith, Austin

doi:10.1101/2020.09.04.283218

Cited by 24 publications

(27 citation statements)

References 124 publications

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“…If these cells do appear it will become possible to identify and capture them in vitro. Mouse formative stem cells can contribute to germline chimeras and can be captured from E5.5 embryos in the presence of low concentration of Activin and inhibition of Wnt and retinoic acid receptor (Kinoshita et al, 2020). These cells exhibit OTX2 expression but lack primitive streak markers T, GSC, and low FOXA2.…”

Section: Reviewmentioning

confidence: 99%

Conserved features of non-primate bilaminar disc embryos and the germline

2021

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Post-implantation embryo development commences with a bilaminar disc in most mammals, including humans. Whereas access to early human embryos is limited and subject to greater ethical scrutiny, studies on non-primate embryos developing as bilaminar discs offer exceptional opportunities for advances in gastrulation, the germline, and the basis for evolutionary divergence applicable to human development. Here, we discuss the advantages of investigations in the pig embryo as an exemplar of development of a bilaminar disc embryo with relevance to early human development. Besides, the pig has the potential for the creation of humanized organs for xenotransplantation. Precise genetic engineering approaches, imaging, and single-cell analysis are cost effective and efficient, enabling research into some outstanding questions on human development and for developing authentic models of early human development with stem cells.

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Section: Reviewmentioning

confidence: 99%

Conserved features of non-primate bilaminar disc embryos and the germline

2021

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“…This rosette-like configuration progresses to then form the mature post-implantation epiblast, a monolayered polarized epithelium surrounding a cavity at its center ( Molè et al., 2020 ). Alongside this substantial morphogenetic transformation, the epiblast undergoes transcriptional changes by dismantling the pluripotency genes of the naive state and acquiring a lineage-biased formative/primed state after implantation ( Boroviak and Nichols, 2017 ; Hackett and Surani, 2014 ; Kinoshita et al., 2020 ; Wu et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Integrin β1 coordinates survival and morphogenesis of the embryonic lineage upon implantation and pluripotency transition

et al. 2021

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Summary At implantation, the embryo establishes contacts with the maternal endometrium. This stage is associated with a high incidence of preclinical pregnancy losses. While the maternal factors underlying uterine receptivity have been investigated, the signals required by the embryo for successful peri-implantation development remain elusive. To explore these, we studied integrin β1 signaling, as embryos deficient for this receptor degenerate at implantation. We demonstrate that the coordinated action of pro-survival signals and localized actomyosin suppression via integrin β1 permits the development of the embryo beyond implantation. Failure of either process leads to developmental arrest and apoptosis. Pharmacological stimulation through fibroblast growth factor 2 (FGF2) and insulin-like growth factor 1 (IGF1), coupled with ROCK-mediated actomyosin inhibition, rescues the deficiency of integrin β1, promoting progression to post-implantation stages. Mutual exclusion between integrin β1 and actomyosin seems to be conserved in the human embryo, suggesting the possibility that these mechanisms could also underlie the transition of the human epiblast from pre- to post-implantation.

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“…In mice, permissiveness for PGC specification is unique to formative epiblast cells (i.e., E5.0-E6.0 epibast, EpiLCs) or PSCs with formative pluripotency 31,[42][43][44] . The primed EpiSCs, which corresponding to E6.5 epiblast, have lost the competence of PGC responsiveness (Ref).…”

Section: Discussionmentioning

confidence: 99%

Single Cell Sequencing Reveals Early PGC-like Intermediates During Mouse Primed to Naïve Transition

Liu

Zhou

et al. 2021

Preprint

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Single cell analysis provides clarity unattainable with bulk approaches. Here we apply single cell RNA-seq to a newly established BMP4 induced mouse primed to naive transition (Bi-PNT) system and show that the reset is not a direct reversal of cell fate but through developmental intermediates. We first show that mEpiSCs bifurcate into c-Kit+ naïve and c-Kit- placenta-like cells, among which, the naive branch undergoes further transition through a primordial germ cell-like cells (PGCLCs) intermediate capable of spermatogenesis in vivo. Indeed, deficiency of Prdm1/Blimp1, the key regulator for PGC specification, blocks the induction of PGCLCs and naïve cells. Instead, Gata2 knockout arrests placenta-like fate, but facilitates the generation of PGCLCs. Our results not only reveal a newly cell fate dynamics between primed and naive states at single-cell resolution, but also provide a model system to explore mechanisms involved in regaining germline competence from primed pluripotency.

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Capture of mouse and human stem cells with features of formative pluripotency

Cited by 24 publications

References 124 publications

Conserved features of non-primate bilaminar disc embryos and the germline

Conserved features of non-primate bilaminar disc embryos and the germline

Integrin β1 coordinates survival and morphogenesis of the embryonic lineage upon implantation and pluripotency transition

Single Cell Sequencing Reveals Early PGC-like Intermediates During Mouse Primed to Naïve Transition

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