The trophectoderm acts as a niche for the inner cell mass through IL-6 signaling [reprogramming_embryo]

IL-6 has been shown to be required for somatic cell reprogramming into induced pluripotent stem cells (iPSCs). However, how the cytokine is regulated and if it plays a role during embryo development remains unknown. Here we describe that IL-6 is strictly necessary for C/EBPa-enhanced reprogramming of B cells into iPSCs but not for B cell to macrophage transdifferentiation. C/EBPa induces the expression of both Il6 and Il6ra genes in B cells and in PSCs. During preimplantation embryo development C/EBPa is expressed in blastocysts where it is required for the maintenance of Il6. The expression of Cebpa is enriched in trophectoderm together with Il6 whereas the receptor gene Il6ra is predominantly expressed in the inner cell mass (ICM), in both mouse and humans. Blastocysts secrete IL-6 and neutralization of the cytokine delays the morula to blastocyst transition. Our study indicates that the trophectoderm acts as a niche for the ICM through the secretion of C/EBPa-regulated IL-6, facilitating efficient blastocyst development. (1) Study of gene expression changes from mRNA of WT and Il6 K.O. B cells during their reprogramming into iPSCs. (2) Gene expression changes from mRNA of Cebpa morulas and blastocysts derived from heterozygous Cebpa crosses.