The progressive failure of muscle repair and an altered inflammatory response can lead to fibrosis that in turn can also negatively influence stem cells functionality.

While fibrosis typically begins as part of the wound healing response, excessive accumulation of collagen and other Extracellular Matrix (ECM) components during chronic injury/inflammation can lead to the destruction of normal tissue architecture and is thought to contribute to age-associated loss of tissue and organ decline.

We will study their fate and the intrinsic/extrinsic mechanisms that regulate fate choices in developing and regenerating muscle. Understanding the nature of stem cells interaction in the niche is indeed an obligatory step toward new approaches in stem cell therapy.

We will use the Tg:TNAP-CRERT mouse or other CRERT mice (e.g. NG2-CRERT) to perform in vivo lineage tracing analysis of pericytes (PC) and myoblasts (MB) during development, in mouse models of muscular dystrophy and mice mutant for genes regulating fibrosis (e.g. TGF-β receptor), both at different times of development, and during disease progression.

Moreover, we will study pPC and skeletal MB contribution to blood vessel wall formation, myofibres and fibrotic tissue. To visualize clonal progeny during development and pathology we will use various CreERT driver on a Rosa Confetti background (at low tamoxifen) to identify histochemically the composition of various clones (myogenic, smooth, fibrotic or endothelial). Finally, sorted populations will be challenged in vitro with different ECM proteins (e.g. laminins, collagens) and signaling molecules (e.g. Noggin, TGF β) to determine which of these molecules (and combination thereof) may promote one cell fate at the expense of the others.