The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency

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• dc.contributor.author Athanasouli, Paraskevi
• dc.contributor.author Balli, Martina
• dc.contributor.author De Jaime-Soguero, Anchel
• dc.contributor.author Boel, Annekatrien
• dc.contributor.author Papanikolaou, Sofia
• dc.contributor.author van der Veer, Bernard K.
• dc.contributor.author Janiszewski, Adrian
• dc.contributor.author Vanhessche, Tijs
• dc.contributor.author Francis, Annick
• dc.contributor.author El Laithy, Youssef
• dc.contributor.author Lo Nigro, Antonio
• dc.contributor.author Aulicino, Francesco, 1987-
• dc.contributor.author Koh, Kian Peng
• dc.contributor.author Pasque, Vincent
• dc.contributor.author Cosma, Maria Pia, 1970-
• dc.contributor.author Verfaillie, Catherine
• dc.contributor.author Zwijsen, An
• dc.contributor.author Heindryckx, Björn
• dc.contributor.author Nikolaou, Christoforos
• dc.contributor.author Lluis Vinas, Frederic
• dc.date.accessioned 2023-06-12T05:39:43Z
• dc.date.available 2023-06-12T05:39:43Z
• dc.date.issued 2023
• dc.description Supplemental material files: supplementary information: online appendix; replication file
• dc.description.abstract Early during preimplantation development and in heterogeneous mouse embryonic stem cells (mESC) culture, pluripotent cells are specified towards either the primed epiblast or the primitive endoderm (PE) lineage. Canonical Wnt signaling is crucial for safeguarding naive pluripotency and embryo implantation, yet the role and relevance of canonical Wnt inhibition during early mammalian development remains unknown. Here, we demonstrate that transcriptional repression exerted by Wnt/TCF7L1 promotes PE differentiation of mESCs and in preimplantation inner cell mass. Time-series RNA sequencing and promoter occupancy data reveal that TCF7L1 binds and represses genes encoding essential naive pluripotency factors and indispensable regulators of the formative pluripotency program, including Otx2 and Lef1. Consequently, TCF7L1 promotes pluripotency exit and suppresses epiblast lineage formation, thereby driving cells into PE specification. Conversely, TCF7L1 is required for PE specification as deletion of Tcf7l1 abrogates PE differentiation without restraining epiblast priming. Taken together, our study underscores the importance of transcriptional Wnt inhibition in regulating lineage specification in ESCs and preimplantation embryo development as well as identifies TCF7L1 as key regulator of this process.
• dc.description.sponsorship We would like to thank Dr. Brad Merrill for providing the WT and Tcf7l1−/− mESCs cells and Samantha Zaunz for helping on FACS experiments. We are grateful to Susan Schlenner and the KU Leuven FACS core team for providing the facility and especially Reena Chinaraj who helped us during flow cytometry experiments. We also thank Lotte Schoeters and Alvaro Cortes Calabuig from the KULeuven Genomics Core (http://genomicscore.be) for RNA sequencing, data processing and analysis. The authors would like to extend their gratitude to the FWO Research Foundation – Flanders for the Ph.D. fellowships awarded to P.A. (11M7822N), B.V. (11E7920N), A.J. (1158318 N), postdoctoral funding to A.B. (1298722 N), KU Postdoctoral Mandate awarded to ADJS (PDM/18/212) and FWO-Vlaanderen Research Project Grants G097618N, G091521N (F.L.L.), G073622N (F.L.L., B.H.), G092518N, G0C6820N (K.P.K.), G0C9320N, G0B4420N (V.P.), EOS grant G0I7822N (V.P.), Ministerio de Ciencia e Innovación 008506-PID2020-114080GB-I00 (M.P.C.) and AGAUR grant 006712 2017-SGR 689 (M.P.C.) and C1 KU Leuven internal grants C14/21/115 (F.L.L.), C14/21/119 (V.P.).
• dc.format.mimetype application/pdf
• dc.identifier.citation Athanasouli P, Balli M, De Jaime-Soguero A, Boel A, Papanikolaou S, van der Veer BK, Janiszewski A, Vanhessche T, Francis A, El Laithy Y, Nigro AL, Aulicino F, Koh KP, Pasque V, Cosma MP, Verfaillie C, Zwijsen A, Heindryckx B, Nikolaou C, Lluis F. The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency. Nat Commun. 2023 Mar 3;14:1210. DOI: 10.1038/s41467-023-36914-1
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-023-36914-1
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/57144
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nature Communications. 2023 Mar 3;14:1210
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-114080GB-I00
• dc.rights © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Embrions
• dc.subject.other Embriologia
• dc.subject.other Cèl·lules mare
• dc.title The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion