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

Plana-Carmona, Marcos; Stik, Gregoire; Bulteau, Romain; Segura-Morales, Carolina; Alcazar, Noelia; Wyatt, Chris DR; Klonizakis, Antonios; ... Graf, Thomas; + view all (2022) The trophectoderm acts as a niche for the inner cell mass through C/EBPa-regulated IL-6 signaling. Stem Cell Reports , 17 (9) pp. 1991-2004. 10.1016/j.stemcr.2022.07.009. Green open access

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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.

Type: Article
Title: The trophectoderm acts as a niche for the inner cell mass through C/EBPa-regulated IL-6 signaling
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.stemcr.2022.07.009
Publisher version: https://doi.org/10.1016/j.stemcr.2022.07.009
Language: English
Additional information: © 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/).
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell & Tissue Engineering, Cell Biology, BINDING PROTEIN-ALPHA, RNA-SEQ, GENE-EXPRESSION, DIFFERENTIATION, IMMUNE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10179570
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