Optical stimulation of the FGF signaling pathway is sufficient to maintain human pluripotent stem cells

Stem cell fate is largely determined by a cell-signaling network and can be controlled by the supplementation of exogenous recombinant proteins; this, however, may cause heterogeneous and unsynchronized signaling due to the uneven distribution of recombinant proteins. Such issues are closely associated with the spontaneous differentiation of human pluripotent stem cells (hPSC), which lead to a continuing loss of pluripotency. We report a novel optical control system to maintain the cellular fate of hPSCs without the daily supplementation of recombinant Fibroblast Growth Factor 2 (FGF2) protein, a key molecule for their stemness. Using blue light illumination, we mimick the activation of the FGF signaling pathway in hPSCs carrying the large light-oxygen-voltage (LOV)-sensing domain, an algae-/plant-derived photo-activable protein. The optically maintained hPSCs have similar cellular and molecular profiles to those cultured with FGF2 protein and display differentiation capabilities into three germ layers. These data provide proof-of-concept that the optical control of signaling pathways can be applied to human stem cells.