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Deciphering Hallmark Combination Distinct for Peri-Implantation Stem Cell Models
33 Pages Posted: 28 Jul 2023 Publication Status: Under Review
More...Abstract
Development of new 2D and 3D models of human development such as trophoblast stem cells, gastruloids or blastoids widened possibilities to study early timepoints of development and brightened up ever so slightly the black box of human development. While opening new horizons, the cell sources of those models need proper benchmarking to clarify which hallmark is associated with which lineage and developmental stage. Here, we propose a thorough characterization of pluripotent and trophoblastic stem cell models by transcriptomic, proteomic, epigenetic and metabolic approaches. Extended pluripotent stem cells are similar to primed pluripotent stem cells for most criteria, except metabolic activity, which might explain their ability to convert directly into trophoblast stem cells. We show that trophoblast stem cells are hypo-methylated and that they have a high metabolic activity. Our results clarify the fact that hallmarks of pluripotency are not predictive of each other and have to be used in combination. Multiplying hallmarks alleviate stage matching bias.
Note:
Funding Information: This work was supported by Theramex and ANR-22-CE91-0010. Research in the Pasque laboratory was supported by the Research Foundation– Flanders (FWO; Odysseus Return Grant G0F7716N to V.P.; FWO grants G0C9320N and G0B4420N to V.P.), FWO EOS grant G0I7822N to V.P. and the KU Leuven Research Fund (C1 grant C14/21/119 to V.P.), and FWO PhD fellowships to R.N.A. (11L0722N). KM was supported by a fellowship from the French Medical Research Foundation (FRM SPF201809006928) and the LabEx ‘Who Am I?’ (ANR-11-LABX-0071). Research in the Rougeulle laboratory was supported by the Agence Nationale pour la Recherche (ANR-14-CE10-0017 and ANR-19-CE12-0018-01) and by Ligue Nationale contre le Cancer.
Declaration of Interests: Authors declare no conflict of interest.
Keywords: Epiblast, trophectoderm, trophoblast, pluripotency, cell fate, peri-implantation development, hallmarks
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