Abstract

Complement C1q plays a key role as a recognition molecule as a part of the immune system, driving autocatalytic complement cascade activation and acting as an opsonin. We have previously reported a non-immune role for complement C1q modulating human neural stem cell (hNSC) migration and fate, however, the mechanism underlying these effects has not been identified. Here we show for the first time that C1q acts as a functional hNSC ligand, inducing intracellular signaling to control cell behavior. Using an unbiased screening strategy, we identify five transmembrane C1q signaling/receptor candidates in hNSC (CD44, GPR62, BAI1, cMET, and ADCY5). We further investigate C1q-CD44 interaction, demonstrating that CD44 mediates C1q induced hNSC signaling and chemotaxis in-vitro, and hNSC migration and functional repair in vivo after spinal cord injury. These experiments reveal a novel receptor-mediated mechanism for C1q modulation of NSC behavior and show that the modification of C1q receptor expression can expand the therapeutic window for hNSC transplantation.