Fig. 1

The diagram for TWEAK/Fn14 axis effects on pluripotent stem cells. TWEAK, binding to the Fn14 receptor on embryonic stem cells (ESCs) or mesenchymal stem cells (MSCs), leads to distinct effects on differentiation. TWEAK acts on ESCs to inhibit Th1 immunity, coronary vessel formation, or heart muscle formation via increased NF-κB and decreased JAK-STAT1 signaling. However, TWEAK promotes MSC differentiation into mesenchymal lineage cells via NF-κB or PI3K/Akt. All the lineage cells, including myoblast, chondrocyte, preadipocyte, fibroblast, and osteoblast, express Fn14 and are TWEAK-responsive. TWEAK administration can induce the mesenchymal lineage cells differentiating into corresponding tissues except for preadipocyte. Akt, protein kinase B; ESCs, embryonic stem cells; Fn14, fibroblast growth factor‐inducible 14; JAK, janus kinase; miR, microRNA; MSCs, mesenchymal stem cells; NK, natural killer; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PI3K, phosphatidylinositol 3-kinase; STAT1, signal transducer and activator of transcription 1; Th1, T helper 1; TWEAK, tumor necrosis factor-like weak inducer of apoptosis