Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair

<jats:p>C1q plays a key role as a recognition molecule in the immune system, driving autocatalytic complement cascade activation and acting as an opsonin. We have previously reported a non-immune role of complement C1q modulating the migration and fate of human neural stem cells (hNSC); however, the mechanism underlying these effects has not yet 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 identified five transmembrane C1q signaling/receptor candidates in hNSC (CD44, GPR62, BAI1, c-MET, and ADCY5). We further investigated the interaction between C1q and CD44 , 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 results reveal a receptor-mediated mechanism for C1q modulation of NSC behavior and show that modification of C1q receptor expression can expand the therapeutic window for hNSC transplantation.</jats:p>

Benavente, F., Piltti, K. M., Hooshmand, M. J., Nava, A. A., Lakatos, A., Feld, B. G., Creasman, D., Gershon, P. D., & Anderson, A. (2020). Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair. eLife, 9, e55732. https://doi.org/10.7554/eLife.55732