Stem Cells in Regeneration of Skeletal Muscle
Skeletal muscle serves a multitude of functions in the organism and exhibits a remarkable ability to adapt to physiological demands. Satellite cells are the stem cells of skeletal muscle and are associated with its growth, maintenance and regeneration. Aged skeletal muscle shows a significantly impaired regenerative potential. Evidence in the literature suggests that functionality of satellite cells in aged skeletal muscle is impaired due to the aged environment, but also due to intrinsic differences between adult and aged satellite cells. Our lab investigates the intrinsic differences between adult and aged satellite cells, especially the satellite stem cell subpopulation. This work will provide insights into pathways, which are perturbed in aged satellite cells and allow for modification of these pathways thereby rejuvenating aged muscle.
To assess the functionality of satellite cells during aging, we analyze injured skeletal muscles from aged and adult mice and investigate the regeneration process at different time points after injury. We could already show that JAK/STAT-signaling is upregulated in aged satellite cells leading to impaired regeneration in aged skeletal muscle.
The ultimate goal in the treatment of sarcopenia – the age-related reduction in muscle mass and functionality – is to preserve muscle mass and restore satellite cell homeostasis. When the homeostasis of a tissue is perturbed this likely leads to its degeneration. A factor that can restore the differentiation potential of satellite cells and their ability to self-renew in the aged has the potential to reinstate tissue homeostasis in old skeletal muscle. Therefore we propose to perform a screen to determine such factors using single fiber cultures from aged mice.
- Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals.
Schwörer S, Becker F, Feller C, Baig AH, Köber U, Henze H, Kraus JM, Xin B, Lechel A, Lipka DB, Varghese CS, Schmidt M, Rohs R, Aebersold R, Medina KL, Kestler HA, Neri F, von Maltzahn** J, Tümpel** S, Rudolph** KL
Nature 2016, 540(7633), 428-32 ** co-corresponding authors
- Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice.
Lukjanenko L, Jung MJ, Hegde N, Perruisseau-Carrier C, Migliavacca E, Rozo M, Karaz S, Jacot G, Schmidt M, Li L, Metairon S, Raymond F, Lee U, Sizzano F, Wilson DH, Dumont NA, Palini A, Fässler R, Steiner P, Descombes P, Rudnicki MA, Fan CM, von Maltzahn J, Feige JN, Bentzinger CF
Nat Med 2016, 22(8), 897-905
- Inhibition of JAK-STAT signaling stimulates adult satellite cell function.
Price* FD, von Maltzahn* J, Bentzinger CF, Dumont NA, Yin H, Chang NC, Wilson DH, Frenette J, Rudnicki MA
Nat Med 2014, 10, 1174-81 * equal contribution, published during change of institution
- A truncated Wnt7a retains full biological activity in skeletal muscle.
von Maltzahn J, Zinoviev R, Chang NC, Bentzinger CF, Rudnicki MA
Nat Commun 2013, 4, 2869 research results from former institution
- Pax7 is critical for the normal function of satellite cells in adult skeletal muscle.
von Maltzahn J, Jones AE, Parks RJ, Rudnicki MA
Proc Natl Acad Sci U S A 2013, 110(41), 16474-9