Gene networks controlling functional cell interactions in the pig embryo revealed by omics studies

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Dufour, Adrien | Kurylo, Cyril | Stöckl, Jan, B | Bailly, Yoann | Manceau, Patrick | Martins, Frédéric | Ferchaud, Stéphane | Pain, Bertrand | Fröhlich, Thomas | Foissac, Sylvain | Artus, Jérôme | Acloque, Hervé

Edité par CCSD -

International audience. Pig embryonic development differs from that of humans and mice from the blastocyst stage and is characterised by a much later implantation. This particular period is associated with a lengthening and significant growth of the extra-embryonic tissues and is still poorly understood. To better understand the biology of the pig blastocyst, we generated a large dataset of single-cell transcriptomics scRNAseq and scATACseq) at different embryonic stages (early, late, ovoid and elongated blastocysts) and the associated proteomic dataset from the corresponding uterine fluids. These data were cleaned, filtered and represent a total of 35,000 cells. Using these data, we first characterised embryonic and extra-embryonic cell populations and their evolution, and identified specific markers of these populations. We then used a pig-adapted version of the SCENIC package to infer gene regulatory networks (regulons) and selected those that were specifically active in each embryonic population. Meta-analysis of other scRNAseq publications on the preimplantation embryo in pigs and humans increased confidence in the regulons we identified. We then linked these regulons to signalling pathways and biological processes. To do this, we used the CellCom software to build signalling networks from ligands (expressed by cells or present in the uterine fluids), receptors, intermediary players, to TF. Thanks to this integrative study, we have identified key new players controlling the biology of the three main cell lineages and identified novel stage-specific subpopulations. Taken together, our work provides new insights into the functional interactions of the first cell lineages within the conceptus prior to implantation.

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