The trophectoderm acts as a niche for the inner cell mass through C/EBPα-regulated IL-6 signaling

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  • dc.contributor.author Plana-Carmona, Marcos
  • dc.contributor.author Stik, Grégoire
  • dc.contributor.author Bulteau, Romain
  • dc.contributor.author Segura-Morales, Carolina
  • dc.contributor.author Alcázar, Noelia
  • dc.contributor.author Wyatt, Christopher Douglas Robert, 1988-
  • dc.contributor.author Klonizakis, Antonios
  • dc.contributor.author Andrés Aguayo, Luisa de
  • dc.contributor.author Gasnier, Maxime
  • dc.contributor.author Tian, Tian V.
  • dc.contributor.author Torcal Garcia, Guillem, 1991-
  • dc.contributor.author Vila-Casadesús, Maria
  • dc.contributor.author Plachta, Nicolas
  • dc.contributor.author Serrano, Manuel
  • dc.contributor.author Francesconi, Mirko
  • dc.contributor.author Graf, T. (Thomas)
  • dc.date.accessioned 2022-11-09T07:25:22Z
  • dc.date.available 2022-11-09T07:25:22Z
  • dc.date.issued 2022
  • dc.description.abstract IL-6 has been shown to be required for somatic cell reprogramming into induced pluripotent stem cells (iPSCs). However, how Il6 expression is regulated and whether it plays a role during embryo development remains unknown. Here, we describe that IL-6 is necessary for C/EBPα-enhanced reprogramming of B cells into iPSCs but not for B cell to macrophage transdifferentiation. C/EBPα overexpression activates both Il6 and Il6ra genes in B cells and in PSCs. In embryo development, Cebpa is enriched in the trophectoderm of blastocysts together with Il6, while Il6ra is mostly expressed in the inner cell mass (ICM). In addition, Il6 expression in blastocysts requires Cebpa. Blastocysts secrete IL-6 and neutralization of the cytokine delays the morula to blastocyst transition. The observed requirement of C/EBPα-regulated IL-6 signaling for pluripotency during somatic cell reprogramming thus recapitulates a physiologic mechanism in which the trophectoderm acts as niche for the ICM through the secretion of IL-6.
  • dc.description.sponsorship Work in the laboratory of T.G. was supported by the Spanish Ministry of Economy, Industry and Competitiveness (Plan Estatal PID2019-109354GB-I00), the CRG, AGAUR (SGR 726), and a European Research Council Synergy grant (4D-Genome). M.P.-C. was supported by an FPI fellowship (BES-2016-076900). Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (SAF2017-82613-R), ERC (ERC-2014-AdG/669622), la Caixa Foundation, and Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement of Catalonia (Grup de Recerca consolidat 2017 SGR 282).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Plana-Carmona M, Stik G, Bulteau R, Segura-Morales C, Alcázar N, Wyatt CDR, Klonizakis A, de Andrés-Aguayo L, Gasnier M, Tian TV, Torcal Garcia G, Vila-Casadesús M, Plachta N, Serrano M, Francesconi M, Graf T. The trophectoderm acts as a niche for the inner cell mass through C/EBPα-regulated IL-6 signaling. Stem Cell Reports. 2022 Sep 13;17(9):1991-2004. DOI: 10.1016/j.stemcr.2022.07.009
  • dc.identifier.doi http://dx.doi.org/10.1016/j.stemcr.2022.07.009
  • dc.identifier.issn 2213-6711
  • dc.identifier.uri http://hdl.handle.net/10230/54769
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Stem Cell Reports. 2022 Sep 13;17(9):1991-2004
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/669622
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-109354GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-82613-R
  • dc.rights © 2022 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword C/EBP transcription factor
  • dc.subject.keyword IL-6 signaling
  • dc.subject.keyword Gene regulation
  • dc.subject.keyword Inner cell mass
  • dc.subject.keyword Pre-implantation embryo development
  • dc.subject.keyword Somatic cell reprogramming
  • dc.subject.keyword Transdifferentiation
  • dc.subject.keyword Trophectoderm
  • dc.title The trophectoderm acts as a niche for the inner cell mass through C/EBPα-regulated IL-6 signaling
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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