Brief report: complement C5a promotes human embryonic stem cell pluripotency in the absence of FGF2.

The complement activation product, C5a, is a pivotal member of the innate immune response; however, a diverse number of nonimmune functions are now being ascribed to C5a signaling, including roles during embryonic development. Here, we identify the expression of the C5a precursor protein, C5, as well as the C5a receptors, C5aR and C5L2, in both human embryonic stem cells and human-induced pluripotent stem cells. We show that administration of a physiologically relevant dose of purified human C5a (1 nM) stimulates activation of ERK1/2 and AKT signaling pathways, and is able to promote maintenance of the pluripotent state in the absence of FGF2. C5a also reduced cell loss following dissociation of human pluripotent stem cells. Our results reveal that complement C5a signaling supports human stem cell pluripotency and survival, and thus may play a key role in shaping early human embryonic development.