Major transcriptomic, epigenetic and metabolic changes underlie the pluripotency continuum in rabbit preimplantation embryos

Bouchereau, Wilhelm; Jouneau, Luc; Archilla, Catherine; Aksoy, Irène; Moulin, Anaïs; Daniel, Nathalie; Peynot, Nathalie; Caldérari, Sophie; Joly, Thierry; Godet, Murielle; Jaszczyszyn, Yan; Pratlong, Marine; Séverac, Dany; Savatier, Pierre; Duranthon, Véronique; Afanassieff, Marielle; Beaujean, Nathalie

doi:10.1242/dev.200538

Cited by 8 publications

(14 citation statements)

References 87 publications

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“…Many of the selected genes have been demonstrated to support naïve pluripotency or facilitate the resetting of naïve-like features when overexpressed in mice and humans (Cartwright et al 2005;Ema et al 2008;Jiang et al 2008;Parisi et al 2008;Bourillot et al 2009;Guo et al 2009;Silva et al 2009;Guo and Smith 2010;Han et al 2010;Lee et al 2012;Nagamatsu et al 2012;Martello et al 2013;Tai and Ying 2013;Uranishi et al 2013;Stuart et al 2014;Takashima et al 2014;Qiu et al 2015;Pastor et al 2018;Festuccia et al 2021;Lea et al 2021). Our RNAseq analyses of rabbit embryos confirmed that all but one gene (GFI1) were expressed in the ICM/early epiblast of day 3 and 4 rabbit blastocysts (Bouchereau et al, 2022) (Fig. S2A).…”

Section: Cdna Library Screeningsupporting

confidence: 55%

Generation of Systemic Chimeras via Rabbit Induced Pluripotent Stem Cells Reprogrammed with KLF2, ERAS, and PRMT6

Perold,

Pham,

Pijoff

et al. 2024

Preprint

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Little is known about the molecular underpinnings of pluripotent stem cells' (PSCs) ability to colonize the epiblast of preimplantation embryos and generate chimeras. In our study, using rabbit PSCs as a model system, we conducted unbiased screening of a cDNA library that encodes a panel of 36 pluripotency factors. From this screening, we identified KLF2, ERAS and PRMT6, whose overexpression confers the ability for self-renewal in a KOSR/FGF2-free culture medium supplemented with LIF, activin A, PKC and WNT inhibitors. The reprogrammed cells acquired transcriptomic and epigenetic features of naive pluripotency, including the reactivation of the 2nd X-chromosome. Leveraging these PSC lines, we determined the transcriptomic signature of embryonic colonization-competence, demonstrating transcriptional repression of genes involved in MAPK, WNT, HIPPO, and EPH signaling pathways, alongside the activation of genes involved in amino-acid metabolism, NF-kB signaling, and p53 pathway. Remarkably, a subset of reprogrammed cells, expressing CD75 at a high level, gained the ability to produce chimeric fetuses with a high contribution from PSCs in all lineages.

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Section: Cdna Library Screeningsupporting

confidence: 55%

Generation of Systemic Chimeras via Rabbit Induced Pluripotent Stem Cells Reprogrammed with KLF2, ERAS, and PRMT6

Perold,

Pham,

Pijoff

et al. 2024

Preprint

Self Cite

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“…The PGC states are associated with high expression levels of TFAP2C, SOX15, SOX17, CITED1, FOXA3, and NANOS3 ( Figure 7A ). Interestingly, SOX15 has been shown to be a primate and rabbit naïve pluripotency TF, though not in mouse 13,40 . Analysis of PS and nascent mesoderm TFs, clearly showed that PGCs from all embryonic stages do not upregulate most canonical TFs, such as T, EOMES, MIXL1, SNAI1 and HOXA1.…”

Section: Resultsmentioning

confidence: 99%

“…Single cell transcriptomics and multi-omics are recently being used to map transcriptional and chromatin states in early embryonic development 7,[12][13][14][15][16][17][18][19][20][21][22] . This resulted in comprehensive atlases that greatly enrich and refine previous imaging-based data by characterizing precisely transcriptional programs at high cellular resolution.…”

Section: Introductionmentioning

confidence: 99%

Time-Aligned Hourglass Gastrulation Models in Rabbit and Mouse

Mayshar

Raz

Cheng

et al. 2022

Preprint

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The hourglass model describes the convergence of species within the same phylum to a similar body plan during development, yet the molecular mechanisms underlying this phenomenon in mammals remain poorly described. Here, we compare rabbit and mouse time-resolved differentiation trajectories to revisit this model at single cell resolution. We modeled gastrulation dynamics using hundreds of embryos sampled between gestation days 6.0-8.5, and compare the species using a new framework for time-resolved single-cell differentiation-flows analysis. We find convergence toward similar cell state compositions at E7.5, underlied by quantitatively conserved expression of 76 transcription factors, despite divergence in surrounding trophoblast and hypoblast signaling. However, we observed noticeable changes in specification timing of some lineages, and divergence of primordial germ cells programs, which in the rabbit do not activate mesoderm genes. Comparative analysis of temporal differentiation models provides a new basis for studying the evolution of gastrulation dynamics across mammals.

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“…Previous work showed that mouse, rabbit, monkey and other species exhibit unique and shared developmental features in gene expression, epigenetic regulation, or as a whole with interspecies chimeras (Simerly et al, 2011; Okamoto et al, 2011; Wu et al, 2016; Nakamura et al, 2016; Fu et al, 2020; Bouchereau et al, 2022). However, little was known about cellular morphogenesis, cleavages, and their variabilities.…”

Section: Discussionmentioning

confidence: 99%

Temporal variability and cell mechanics control robustness in mammalian embryogenesis

Fabrèges

Corominas-Murtra

Moghe

et al. 2023

Preprint

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How living systems achieve precision in form and function despite their intrinsic stochasticity is a fundamental yet open question in biology. Here, we establish a quantitative morphomap of pre-implantation embryogenesis in mouse, rabbit and monkey embryos, which reveals that although blastomere divisions desynchronise passively without compensation, 8-cell embryos still display robust 3D structure. Using topological analysis and genetic perturbations in mouse, we show that embryos progressively change their cellular connectivity to a preferred topology, which can be predicted by a simple physical model where noise and actomyosin-driven compaction facilitate topological transitions lowering surface energy. This favours the most compact embryo packing at the 8- and 16-cell stage, thus promoting higher number of inner cells. Impairing mitotic desynchronisation reduces embryo packing compactness and generates significantly more cell mis-allocation and a lower proportion of inner-cell-mass-fated cells, suggesting that stochasticity in division timing contributes to achieving robust patterning and morphogenesis.

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Major transcriptomic, epigenetic and metabolic changes underlie the pluripotency continuum in rabbit preimplantation embryos

Cited by 8 publications

References 87 publications

Generation of Systemic Chimeras via Rabbit Induced Pluripotent Stem Cells Reprogrammed with KLF2, ERAS, and PRMT6

Generation of Systemic Chimeras via Rabbit Induced Pluripotent Stem Cells Reprogrammed with KLF2, ERAS, and PRMT6

Time-Aligned Hourglass Gastrulation Models in Rabbit and Mouse

Temporal variability and cell mechanics control robustness in mammalian embryogenesis

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