Mouse embryonic stem cells derived from the epiblast1 contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm2 upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species.

Inflammatory bowel disease is an immune-mediated intestinal inflammatory condition that is associated with an increase in autoantibodies that bind to epithelial cells. However, it is unknown whether the epithelial cell-derived products that are recognized by such autoantibodies are involved in the pathogenic process. Through a combined antigen-screening approach utilizing humoral and cellular immune responses, we identify herein an epithelial lectin, galectin-4, that specifically stimulates IL-6 production by CD4(+) T cells. Interestingly, the reactivity of CD4(+) T cells to galectin-4 is precisely elicited under intestinal inflammatory conditions. The galectin-4-mediated production of IL-6 is MHC class II independent and induced by PKCtheta-associated pathway through the immunological synapse. The galectin-4-mediated stimulation of CD4(+) T cells is shown to exacerbate chronic colitis and delay the recovery from acute intestinal injury. These studies identify the presence of an immunogenic, endogenous lectin in the intestine and dissect the biological role of lectin/CD4(+) T cell interactions under inflammatory conditions.

Photoinduced decarboxylative radical reactions of benzoic acids with electron-deficient alkenes, diborane, and acetonitrile under organic photoredox catalysis conditions and mild heating afforded adducts, arylboronate esters, and the reduction product, respectively. The reaction is thought to involve single-electron transfer promoted the generation of aryl radicals via decarboxylation. A diverse range of benzoic acids were found to be suitable substrates for this photoreaction. Only our two-molecule organic photoredox system can work well for the direct photoinduced decarboxylation of benzoic acids.