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Excited to share our latest paper just published in #skeletalmuscle!
“Exercise promotes satellite cell contribution to myofibers in a load-dependent manner”
…https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/s13395-020-00237-2
Here are some key takeaways (thread):
#myotwitter
“Exercise promotes satellite cell contribution to myofibers in a load-dependent manner”
…https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/s13395-020-00237-2
Here are some key takeaways (thread):
#myotwitter
We wanted to study how exercise at different mechanical loads drive satellite cell (SC) contribution to myonuclei (SC fusion).
To do this, mice got access to a running wheel which had no resistance or incremental resistance. The increased resistance led to a lower running distance, but substantially higher external work.
As published before, this led to hypertrophy of predominantly the plantar flexors (soleus, plantaris), but not of the dorsiflexors (EDL, tibialis anterior).
We think that this is because dorsiflexors are insufficently loaded during wheel running.
We think that this is because dorsiflexors are insufficently loaded during wheel running.
To assess satellite cell fusion we used Pax7Cre; RosamTmG mice which ubiquitously express membrane-bound Tom, but following tamoxifen injection, Cre-mediated recombination results in the excision of mTom and expression of mGFP in SCs.
In these mice, the presence of GFP+ myofibers indicates that at least one SC fused with those myofibers.
Indeed, after 8-weeks of voluntary running these mice showed a clear load-dependent increase in SC fusion, which was especially apparent in soleus and plantaris.
Indeed, after 8-weeks of voluntary running these mice showed a clear load-dependent increase in SC fusion, which was especially apparent in soleus and plantaris.
Interestingly, also free voluntary running (which did not induce hypertrophy), showed robust SC fusion suggesting that SC fusion can be uncoupled of muscle hypertrophy under specific conditions.
It is not all hypertrophy guys
It is not all hypertrophy guys
To back these data up, we use a Pax7 nuclear reporter mouse (Pax7Cre;RosantdTom) in which the SCs and their derivative nuclei become ntdTom positive (red).
Intriguingly, this model was not adequate as the ntdTom protein can travel between nuclei.
Intriguingly, this model was not adequate as the ntdTom protein can travel between nuclei.
(also shown by this paper) https://www.pnas.org/content/117/6/2978).
Bottom line, watch out with using nuclear reporter mice in exercise settings.
Bottom line, watch out with using nuclear reporter mice in exercise settings.
Finally, we extracted nuclei for exercised and non-exercised mice and used a PCR on genomic DNA to measure Cre-med recombination.
Just like our mTmG model we found load dependent SC fusion: 20% recomb (!) after 8-w of resistance running, while only 12% / 4% in free run and sed.
Just like our mTmG model we found load dependent SC fusion: 20% recomb (!) after 8-w of resistance running, while only 12% / 4% in free run and sed.
More details about fiber type specific SC hypertrophy and fusion + additional in vitro work on nuclear travelling of proteins can be found in the paper.
Thanks to all co-authors for making this possible and especially to @debocklab for motivating me to look at things from a different perspective and to set aside my biases. 
PS: Having a shared first authorship with you future wife ( @EviMasschelein) must be the ultimate relationship I recon. 
Relationship test *
