The interferon γ pathway enhances pluripotency and X-chromosome reactivation in iPSC reprogramming

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  • dc.contributor.author Barrero Asencio, Mercedes
  • dc.contributor.author Lazarenkov, Aleksey
  • dc.contributor.author Blanco, Enrique
  • dc.contributor.author Palma, Luis G.
  • dc.contributor.author López Rubio, Anna V.
  • dc.contributor.author Bauer, Moritz, 1987-
  • dc.contributor.author Bigas Salvans, Anna
  • dc.contributor.author Di Croce, Luciano
  • dc.contributor.author Sardina, Jose Luis
  • dc.contributor.author Payer, Bernhard
  • dc.date.accessioned 2024-12-02T07:17:19Z
  • dc.date.available 2024-12-02T07:17:19Z
  • dc.date.issued 2024
  • dc.description.abstract Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) requires activation of the pluripotency network and resetting of the epigenome by erasing the epigenetic memory of the somatic state. In female mouse cells, a critical epigenetic reprogramming step is the reactivation of the inactive X chromosome. Despite its importance, a systematic understanding of the regulatory networks linking pluripotency and X-reactivation is missing. Here, we reveal important pathways for pluripotency acquisition and X-reactivation using a genome-wide CRISPR screen during neural precursor to iPSC reprogramming. In particular, we discover that activation of the interferon γ (IFNγ) pathway early during reprogramming accelerates pluripotency acquisition and X-reactivation. IFNγ stimulates STAT3 signaling and the pluripotency network and leads to enhanced TET-mediated DNA demethylation, which consequently boosts X-reactivation. We therefore gain a mechanistic understanding of the role of IFNγ in reprogramming and X-reactivation and provide a comprehensive resource of the molecular networks involved in these processes.
  • dc.description.sponsorship This work was supported by Agencia Estatal de Investigación (AEI) of the Spanish Ministry of Science and Innovation (MCIN) and Fondo Europeo de Desarrollo Regional (FEDER) of the European Union grant BFU2017-88407-P (B.P.); AEI of MCIN grant EUR2019-103817/AEI/10.13039/501100011033 (B.P.); grant PID2021-123383NB-I00 funded by MCIN/AEI/10.13039/501100011033/FEDER, UE (B.P.); AEI of MCIN grant PID2019-111243RA-I00 (J.L.S.); AEI of MCIN grant PID2022-142679NB-I00 (L.D.C.); AXA Research Fund (B.P.); Agencia de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) 2017 grant SGR 346 (B.P.); AGAUR 2021 grant SGR 01222 (B.P.); Instituto de Salud Carlos III grant CP19/00176 (J.L.S.); Worldwide Cancer Research 20-0269 (J.L.S.); Ramón Areces Foundation (Doctoral Thesis in Life Sciences Fellowship) (M. Barrero); and La Caixa International PhD Fellowship Program (M. Bauer).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Barrero M, Lazarenkov A, Blanco E, Palma LG, López-Rubio AV, Bauer M, et al. The interferon γ pathway enhances pluripotency and X-chromosome reactivation in iPSC reprogramming. Sci Adv. 2024 Aug 9;10(32):eadj8862. DOI: 10.1126/sciadv.adj8862
  • dc.identifier.doi http://dx.doi.org/10.1126/sciadv.adj8862
  • dc.identifier.issn 2375-2548
  • dc.identifier.uri http://hdl.handle.net/10230/68874
  • dc.language.iso eng
  • dc.publisher American Association for the Advancement of Science (AAAS)
  • dc.relation.ispartof Sci Adv. 2024 Aug 9;10(32):eadj8862
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-123383NB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-111243RA-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-142679NB-I00
  • dc.rights Copyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Cèl·lules mare adultes
  • dc.subject.other Cromosoma X
  • dc.title The interferon γ pathway enhances pluripotency and X-chromosome reactivation in iPSC reprogramming
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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