BENAVENTE PEREZ, FRANCISCA
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BENAVENTE PEREZ, FRANCISCA
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Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair

2020 , BENAVENTE PEREZ, FRANCISCA , Katja M Piltti , Mitra J Hooshmand , Aileen A Nava , Anita Lakatos , Brianna G Feld , Dana Creasman , Paul D Gershon , Aileen Anderson

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.

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