Wagers Lab

Building on our work in mice with Duchenne muscular dystrophy, our group used an adeno-associated virus (AAV) as a transport vehicle to deliver gene-editing cargo rapidly into several different types of skin, blood, and muscle stem and progenitor cells.

Our proof of concept study employed a reporter system, looking at to stem cells in skeletal muscle, skin progenitor cells, and bone marrow. We demonstrated that we can permanently modify the genome of stem cells, and therefore their progenies, in their normal anatomical niche.

The AAV approach we developed makes it possible to investigate the importance of different genes for stem cells in their native environment, much more quickly than ever before. Because the delivery system is so robust, it can also be used to target genes that affect many different tissues.

We are expanding this work, which has implications for the development of therapies for diseases like spinal muscular atrophy.

Our studies have identified novel regulators of stem cell trafficking, including the transcription factor EGR1, which uniquely co-ordinates the migration and proliferation of blood stem cells in order to maintain appropriate stem cell number in the bone marrow and to support peripheral immune and inflammatory responses.

We developed and applied marker-based cell sorting approaches to analyze precursor cells in skeletal muscle, and identified a subset of satellite cells (mononuclear cells found beneath the basal lamina surrounding mature muscle fibers) that act as muscle stem cells. We demonstrated that these unique stem cells exhibit robust self-renewal and myogenic differentiation activity, and can restore muscle function when transplanted into injured or diseased muscle.