Aileen Anderson, The Regents of the University of California, Irvine, United States

Modulation of C1q receptor signalling in NSC to rescue regenerative potential in the SCI niche

Funded in: 2018, 2019, 2020


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Problem: High C1q concentrations impede the proliferation of NSCs

Target: Modulation of C1q receptor signalling in NSC

Goal: Generate therapeutic stem cell population that has greater efficacy after transplantation into the injured spinal cord

 

We have shown that immune molecules play an important role in neural stem cell decisions about where to go (migration) and what to do (fate and integration), and that this is an important variable for the capacity of these cells to drive repair and recovery of function. Here, we hypothesize that high concentrations of a molecule called C1q at the spinal cord injury epicenter and adjacent spared tissue causes neural stem cells to stop proliferating, undergo cell cycle arrest, and fail to differentiate. This proposal therefore tests the mechanisms for these effects, focusing on novel C1q receptors that we have identified to be uniquely expressed by neural stem cells. We test the role of these receptors in changing neural stem cell responses to C1q both in vitro and in vivo after therapeutic transplantation in animal models of spinal cord injury. To do this, we use a combination of transgenic models and gene editing of human neural stem cells. Our goal is to generate and test a therapeutic stem cell population that has greater efficacy after transplantation into the injured spinal cord.