Barrero Asencio, MercedesLazarenkov, AlekseyBlanco, EnriquePalma, Luis G.López Rubio, Anna V.Bauer, Moritz, 1987-Bigas Salvans, AnnaDi Croce, LucianoSardina, Jose LuisPayer, Bernhard2024-12-022024-12-022024Barrero 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.adj88622375-2548http://hdl.handle.net/10230/68874Reprogramming 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.application/pdfengCopyright © 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.Cèl·lules mare adultesCromosoma XThe interferon γ pathway enhances pluripotency and X-chromosome reactivation in iPSC reprogramminginfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1126/sciadv.adj8862info:eu-repo/semantics/openAccess