Wnt4 from the Niche Controls the Mechano-Properties and Quiescent State of Muscle Stem Cells

Satellite cells are skeletal muscle stem cells that facilitate muscle repair and regeneration after “damage” which occurs after physiological stimuli: exercise, post-training micro-injuries and electrical stimulation. Exercise stimuli lead to activation and proliferation of these cells from their quiescent state, therefore, increasing cell numbers having the potential to provide additional myonuclei to their parent muscle fibre or return to a quiescent state. Different exercise modalities are the focus of numerous studies on satellite cells activation. An increase in muscle activity augments satellite cells proliferation as well as skeletal muscle mass and function, both in young and elderly. This review provides an updated view of the contribution of skeletal muscle satellite cells in regulating skeletal muscle mass and the efficiency of the exercise intervention to attenuate the decline in muscle mass.

Download Full-text

Faculty Opinions recommendation of Wnt4 from the Niche Controls the Mechano-Properties and Quiescent State of Muscle Stem Cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736576495.793566387 ◽

2019 ◽

Author(s):

James Tidball

Keyword(s):

Stem Cells ◽

Quiescent State ◽

Muscle Stem Cells

Download Full-text

Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila

eLife ◽

10.7554/elife.08497 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 20

Author(s):

Rajaguru Aradhya ◽

Monika Zmojdzian ◽

Jean Philippe Da Ponte ◽

Krzysztof Jagla

Keyword(s):

Stem Cells ◽

Fruit Fly ◽

Quiescent State ◽

Homing Behavior ◽

Muscle Stem Cells ◽

Dormant State ◽

Adult Muscle ◽

Drosophila Model ◽

Activated State

How stem cells specified during development keep their non-differentiated quiescent state, and how they are reactivated, remain poorly understood. Here, we applied a Drosophila model to follow in vivo behavior of adult muscle precursors (AMPs), the transient fruit fly muscle stem cells. We report that emerging AMPs send out thin filopodia that make contact with neighboring muscles. AMPs keep their filopodia-based association with muscles throughout their dormant state but also when they start to proliferate, suggesting that muscles could play a role in AMP reactivation. Indeed, our genetic analyses indicate that muscles send inductive dIlp6 signals that switch the Insulin pathway ON in closely associated AMPs. This leads to the activation of Notch, which regulates AMP proliferation via dMyc. Altogether, we report that Drosophila AMPs display homing behavior to muscle niche and that the niche-driven Insulin-Notch-dMyc cascade plays a key role in setting the activated state of AMPs.

Download Full-text

Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency

eLife ◽

10.7554/elife.15461 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 7

Author(s):

Sheryl Southard ◽

Ju-Ryoung Kim ◽

SiewHui Low ◽

Richard W Tsika ◽

Christoph Lepper

Keyword(s):

Stem Cells ◽

Muscle Pathology ◽

Quiescent State ◽

Dystrophic Muscle ◽

Cell Hyperplasia ◽

Muscle Stem Cells ◽

Downstream Effectors ◽

Dystrophin Deficiency ◽

Mechanistic Basis ◽

Tissue Restoration

When unperturbed, somatic stem cells are poised to affect immediate tissue restoration upon trauma. Yet, little is known regarding the mechanistic basis controlling initial and homeostatic ‘scaling’ of stem cell pool sizes relative to their target tissues for effective regeneration. Here, we show that TEAD1-expressing skeletal muscle of transgenic mice features a dramatic hyperplasia of muscle stem cells (i.e. satellite cells, SCs) but surprisingly without affecting muscle tissue size. Super-numeral SCs attain a ‘normal’ quiescent state, accelerate regeneration, and maintain regenerative capacity over several injury-induced regeneration bouts. In dystrophic muscle, the TEAD1 transgene also ameliorated the pathology. We further demonstrate that hyperplastic SCs accumulate non-cell-autonomously via signal(s) from the TEAD1-expressing myofiber, suggesting that myofiber-specific TEAD1 overexpression activates a physiological signaling pathway(s) that determines initial and homeostatic SC pool size. We propose that TEAD1 and its downstream effectors are medically relevant targets for enhancing muscle regeneration and ameliorating muscle pathology.

Download Full-text

Fasting Induces a Highly Resilient Deep Quiescent State in Muscle Stem Cells via Ketone Body Signaling

10.1101/2022.01.04.474961 ◽

2022 ◽

Author(s):

Daniel I Benjamin ◽

Pieter I Both ◽

Joel S Benjamin ◽

Christopher W Nutter ◽

Jenna H Tan ◽

...

Keyword(s):

Stem Cells ◽

Muscle Regeneration ◽

Ketone Body ◽

Ketone Bodies ◽

Quiescent State ◽

Muscle Repair ◽

Short Term ◽

Muscle Stem Cells ◽

P53 Activation ◽

Metabolic Mechanism

Short-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet, or exogenously administered, promotes a deep quiescent state in muscle stem cells(MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Further, we show that ketone bodies, specifically b hydroxybutyrate, directly promote MuSC deep quiescence via a non-metabolic mechanism. We show that b-hydroxybutyrate functions as an HDAC inhibitor within MuSCs leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting.

Download Full-text