Unraveling hallmark suitability for staging pre- and post-implantation stem cell models
Constance Onfray,
Simon Chevolleau,
Eva Moinard,
Océane Girard,
Kasturi Mahadik,
Ryan Allsop,
Grigorios Georgolopoulos,
Régis Lavigne,
Ophélie Renoult,
Irene Aksoy,
Elsa Lemaitre,
Philippe Hulin,
Jean-François Ouimette,
Thomas Fréour,
Claire Pecqueur,
Charles Pineau,
Vincent Pasque,
Claire Rougeulle,
Laurent David
Affiliations
Constance Onfray
Nantes Université, CHU Nantes, Inserm, CR2TI, 44000 Nantes, France
Simon Chevolleau
Nantes Université, CHU Nantes, Inserm, CR2TI, 44000 Nantes, France
Eva Moinard
Nantes Université, CHU Nantes, Inserm, CR2TI, 44000 Nantes, France
Océane Girard
Nantes Université, CHU Nantes, Inserm, CR2TI, 44000 Nantes, France
Kasturi Mahadik
Université Paris Cité, CNRS, Epigenetics and Cell Fate, 75013 Paris, France
Ryan Allsop
KU Leuven – University of Leuven, Department of Development and Regeneration, Leuven Institute for Single Cell Omics and Leuven Stem Cell Institute, Herestraat 49, 3000 Leuven, Belgium
Grigorios Georgolopoulos
KU Leuven – University of Leuven, Department of Development and Regeneration, Leuven Institute for Single Cell Omics and Leuven Stem Cell Institute, Herestraat 49, 3000 Leuven, Belgium
Régis Lavigne
University Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) – UMR_S 1085, 35000 Rennes, France; University Rennes, CNRS, Inserm, Biosit UAR 3480 US_S 018, Protim Core Facility, 35000 Rennes, France
Ophélie Renoult
Nantes Université, CNRS, Inserm, CRCI2NA, 44000 Nantes, France
Irene Aksoy
University Lyon, Université Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France
Université Paris Cité, CNRS, Epigenetics and Cell Fate, 75013 Paris, France
Thomas Fréour
Nantes Université, CHU Nantes, Inserm, CR2TI, 44000 Nantes, France; Department of Obstetrics, Gynecology and Reproductive Medicine, Dexeus University Hospital, 08028 Barcelona, Spain; CHU Nantes, Service de Biologie de la Reproduction, 44000 Nantes, France
Claire Pecqueur
Nantes Université, CNRS, Inserm, CRCI2NA, 44000 Nantes, France
Charles Pineau
University Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) – UMR_S 1085, 35000 Rennes, France; University Rennes, CNRS, Inserm, Biosit UAR 3480 US_S 018, Protim Core Facility, 35000 Rennes, France
Vincent Pasque
KU Leuven – University of Leuven, Department of Development and Regeneration, Leuven Institute for Single Cell Omics and Leuven Stem Cell Institute, Herestraat 49, 3000 Leuven, Belgium
Claire Rougeulle
Université Paris Cité, CNRS, Epigenetics and Cell Fate, 75013 Paris, France
Summary: The advent of novel 2D and 3D models for human development, including trophoblast stem cells and blastoids, has expanded opportunities for investigating early developmental events, gradually illuminating the enigmatic realm of human development. While these innovations have ushered in new prospects, it has become essential to establish well-defined benchmarks for the cell sources of these models. We aimed to propose a comprehensive characterization of pluripotent and trophoblastic stem cell models by employing a combination of transcriptomic, proteomic, epigenetic, and metabolic approaches. Our findings reveal that extended pluripotent stem cells share many characteristics with primed pluripotent stem cells, with the exception of metabolic activity. Furthermore, our research demonstrates that DNA hypomethylation and high metabolic activity define trophoblast stem cells. These results underscore the necessity of considering multiple hallmarks of pluripotency rather than relying on a single criterion. Multiplying hallmarks alleviate stage-matching bias.