8C-like cells capture the human zygotic genome activation program in vitro

Taubenschmid-Stowers, Jasmin; Rostovskaya, Maria; Santos, Fátima; Ljung, Sebastian; Argelaguet, Ricard; Krueger, Felix; Nichols, Jennifer; Reik, Wolf

doi:10.1016/j.stem.2022.01.014

Cited by 102 publications

(98 citation statements)

References 70 publications

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“…These 8CLCs represent ∼0.3% of the total cells, consistent with the described proportion of 2CLCs in mouse cultures (Macfarlan et al, 2012). This discovery is in line with the recent description of an analogous 8CLCs population in hESCs cultured naïve PXGL medium (Taubenschmid-Stowers et al, 2022). This observation is a further demonstration of the analogy of hiPSC with hESCs and opens the door to the use of naïve PSCs as a model to study key pathways determining the origin and developmental potential of 8CLCs.…”

Section: Discussionsupporting

confidence: 89%

Revealing cell populations catching the early stages of the human embryo development in naïve pluripotent stem cells

Moya-Jódar

Ullate-Agote

Barlabé

et al. 2022

Preprint

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Little is known about the heterogeneity existent in human naive pluripotent stem cell (hPSC) cultures. In this study, we applied single-cell RNA sequencing to define heterogeneous cell populations present in human naive 5iLAF cultures. While Epiblast-like cells represented the main cell population, noteworthily we detected a population with a trophectoderm-like gene expression profile, which could be subclustered according to three different stages of early trophectoderm maturation. Furthermore, we provided evidence for the existence of an 8-cell-like cell population, equivalent to the 8-cell human embryo. Thus, the 5iLAF naive culture condition emerges as an excellent system to model gene regulation in the earliest stages of human embryogenesis, including zygotic genome activation, circumventing the inaccessibility and ethical issues inherent in the use of human embryos.

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Section: Discussionsupporting

confidence: 89%

Revealing cell populations catching the early stages of the human embryo development in naïve pluripotent stem cells

Moya-Jódar

Ullate-Agote

Barlabé

et al. 2022

Preprint

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“…Moreover, as an endogenous extracellular epitope, NaPi2b staining allows enrichment of the iBM cells without the need for a transgenic reporter construct. We envision that NaPi2b may be of use for isolating and culturing human eight-cell-like cells that were recently discovered among naive hESCs ( Taubenschmid-Stowers et al., 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Transient DUX4 expression in human embryonic stem cells induces blastomere-like expression program that is marked by SLC34A2

Yoshihara¹,

Kirjanov²,

Nykänen³

et al. 2022

Stem Cell Reports

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“…However, the detailed function of DPPA2 in pig embryonic development requires further study. ZSCAN4 is well known as a marker of ZGA in humans ( 56 ) and mice ( 57 ). The role of ZSCAN4 in early embryonic development in cattle ( 58 ) and sheep ( 59 ) has also been reported.…”

Section: Discussionmentioning

confidence: 99%

Arginine Regulates Zygotic Genome Activation in Porcine Embryos Under Nutrition Restriction

et al. 2022

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Arginine has a positive effect on pre-implantation development in pigs. However, the exact mechanism by which arginine promotes embryonic development is undefined. Here, single-cell RNA sequencing technology was applied to porcine in vivo pre-implantation embryos from the zygote to morula stage, it was found that that the expression of arginine metabolism-related genes clearly changed from the 2-cell stage to the 4-cell stage, when zygotic genome activation (ZGA) occurs in porcine embryos. Further analysis showed that arginine metabolism-related genes are significantly correlated with key ZGA genes. To determine the function of arginine in porcine embryos during ZGA, the in vitro fertilization embryos were cultured in PZM-3 medium (0.12 mM arginine, Control group), a modified PZM-3 medium (0 mM arginine, Block group) and a modified PZM-3 medium supplemented with arginine (0.12 mM arginine, Block + Arg group). The results showed that the 4-cell arrest rate was significantly increased in the Block group compared to the Control group (P < 0.05). The 4-cell arrest rate in the Block + Arg group was significantly decreased than that in the Block group (P < 0.05). Meanwhile, the expression of ZGA marker genes and SIRT1 protein in 4-cell embryos was significantly decreased in the Block group compared to the Control group, and their expression was significantly increased in the Block + Arg group. In addition, we observed that the glutathione (GSH), ATP levels, and lipid droplet contents were significantly increased, and the reactive oxygen species (ROS) level was decreased in the Block + Arg group compared to the Block group. Compared with Control group, spermine content in culture medium and the mRNA expression of ornithine decarboxylase1 (ODC1) of embryos in the Block group were significantly decreased (P < 0.05), and those in the Block + Arg group were significantly increased compared with the Block group (P < 0.05). Moreover, when difluoromethylornithine (an inhibitor of ODC1) was added to the modified PZM-3 medium supplemented with arginine, the effect of arginine on ZGA was inhibited. In summary, our findings demonstrated that arginine may regulate ZGA under nutrition restriction in porcine embryos by promoting polyamine synthesis.

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8C-like cells capture the human zygotic genome activation program in vitro

Cited by 102 publications

References 70 publications

Revealing cell populations catching the early stages of the human embryo development in naïve pluripotent stem cells

Revealing cell populations catching the early stages of the human embryo development in naïve pluripotent stem cells

Transient DUX4 expression in human embryonic stem cells induces blastomere-like expression program that is marked by SLC34A2

Arginine Regulates Zygotic Genome Activation in Porcine Embryos Under Nutrition Restriction

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