In many tissues, wound healing and regeneration depends on stem cells to replace the lost or damaged cells. In injured skeletal muscle, a dedicated muscle stem cell population gives rise to new muscle myofibers after an acute injury. In chronic diseases, however, muscle regeneration fails and healthy muscle is gradually replaced with fibrotic scar and fat tissue, a process called fatty fibrosis. This fatty fibrosis of muscle is a prominent feature of chronic muscle diseases such as Duchenne muscular dystrophy (DMD), sarcopenia (age-related loss of skeletal muscle and strength), obesity and diabetes. There are no cures for DMD and no specific therapies for either DMD or sarcopenia.
Coordinating cell-cell interactions is critical for regenerating complex tissues after injury or disease. Primary cilia are small, immotile, microtubule-based cell projections and have evolved to receive and interpret extracellular cues. Cilia play a crucial role in intercellular communication during development and defects in cilia lead to embryonic lethality in both mice and humans. While cilia are present on the majority of cells in our body, we know little about how they function or participate in the repair of adult tissues.
We recently discovered that cilia coordinate muscle repair by controlling the communication between the muscle stem cell population and its support cells. Our lab is now building on this work by investigating how ciliary signaling coordinates cellular communication between stem cells and their niche, to understand how cilia-based communication goes awry in disease and to identify novel pharmacological tools to combat cilia-associated diseases such as fatty fibrosis.
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