This last week was rich in scientific events in the field of stem cells and human embryonic development, with two seminars offered on Thursday December 14 and Friday December 15 in Nantes.

Research in this area is limited by access to human embryos and the difficulties inherent in their manipulation. There is therefore a growing requirement for relevant and, above all, well-characterized substitution models for use adapted to the research questions asked. Harunobu Kagawa (IMBA, Vienna) and Constance Onfray (CR2TI, Nantes) each presented their work and contributions on the development of stem cell and organoid models, allowing a better understanding of the molecular mechanisms at play in peri-implantation development.

Thursday, the Dr. Harunobu Kagawa gave a conference on the development of a blastoid model representing the pre-implantation blastocyst stage, having the capacity to produce the 3 embryonic lineages (epiblast, trophectoderm and primitive endoderm). With the collaboration of Laurent David's team from CR2TI, Dr Kagawa demonstrated that this blastoid model recapitulated the properties of blastocysts, in particular through the comparative analysis of their respective transcriptomes.

Having also developed an in vitro implantation model, he was also able to establish the capacity of blastoids to implant in the endometrium under hormonal stimulation, then to develop and continue their maturation, by following their evolution by video -microscopy. This work has demonstrated that interactions between the trophectoderm and the epiblast are essential for this implantation.

The model thus established and characterized could then be used to identify the molecular pathways involved in development and post-implantation maturation, including the mTOR pathway and protein translation. An analogy with the diapause process in certain mammals has been outlined.

This model opens up exciting new perspectives for understanding human embryonic development.

Friday is Constance Onfray of CR2TI who presented his thesis work on the characterization of the different stages of pluripotency of stem cells, aiming to establish standards for adapted and concerted use by researchers in the field:

• Naive pluripotent stem cells (NPSC), pre-implantation, at the origin of embryonic and extra-embryonic cells;
• Post-implantation “primed” pluripotent stem cells (PPSC), originating from embryonic cells only (epiblast-like);
• Post-implantation “extended” pluripotent stem cells (EPSCs), chemically manipulated to exhibit embryonic and extra-embryonic competence,
• Trophoblastic stem cells (TSC), originating from extra-embryonic cells only.

Constance carried out a comparison of the properties of these different stages of pluripotency, through a transcriptomic profile, but also an analysis of the methylation state of their DNA, the activation/inactivation state of the X chromosome and finally their metabolism. These analyzes were coupled with a mass spectrometry study in collaboration with the core facility protim. His work shows that only a combination of pluripotency markers (transcriptome, epigenetics, metabolism, proteomics) allows a complete and detailed characterization of the different stages: each lineage and each stage of development can be associated with a precise combination of markers.

These studies will make it possible to better choose the stem cell model adapted to the questions asked. They thus contribute to the advancement of knowledge in the field of human development, and therefore to the improvement of fertilization techniques. vitro.

For more information on Harunobu Kagawa’s work:

• Castel G, Meistermann D, Bretin B, Firmin J, Blin J, Loubersac S, Bruneau A, Chevolleau S, Kilens S, Chariau C, Gaignerie A, Francheteau Q, Kagawa H, Charpentier E, Flippe L, Campion V, Haider S , Dietrich B, Kno ̈fler M, Arima T, Bourdon J, Rivron N, Masson D, Fournier T, Okae H, Freour T, and David L. Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells. Cell Reports, 33, 108419, 2020. DOI: 10.1016/j.celrep.2020.108419
• Kagawa H*, Javali A*, Khoei H*, Sommer TM, Sestini G, Novatchkova M, Scholte Op Reimer Y, Castel G, Bruneau A, Maenhoudt N, Lammers J, Loubersac S, Freour T, Vankelecom H, David L, Rivron N. Human blastoids model blastocyst development and implantation. Nature, Published online December 2, 2021. DOI: 10.1038/s41586-021-04267-8

And on the work of Constance Onfray:

– https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4521994