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Dynamical modeling reveals RNA decay mediates the effect of matrix stiffness on aged muscle stem cell fate
Dynamical modeling reveals RNA decay mediates the effect of matrix stiffness on aged muscle stem cell fate
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Length:
20 minutes
Released:
Feb 25, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.02.24.529950v1?rss=1
Authors: Hettinger, Z. R., Hu, S., Mamiya, H., Sahu, A., Iijima, H., Wang, K., Gilmer, G., Miller, A., Nasello, G., D'Amore, A., Vorp, D., Rando, T. A., Xing, J., Ambrosio, F.
Abstract:
Loss of muscle stem cell (MuSC) self-renewal with aging reflects a combination of influences from the intracellular (e.g., post-transcriptional modifications) and extracellular (e.g., matrix stiffness) environment. Whereas conventional single cell analyses have revealed valuable insights into factors contributing to impaired self-renewal with age, most are limited by static measurements that fail to capture nonlinear dynamics. Using bioengineered matrices mimicking the stiffness of young and old muscle, we showed that while young MuSCs were unaffected by aged matrices, old MuSCs were phenotypically rejuvenated by young matrices. Dynamical modeling of RNA velocity vector fields in silico revealed that soft matrices promoted a self-renewing state in old MuSCs by attenuating RNA decay. Vector field perturbations demonstrated that the effects of matrix stiffness on MuSC self-renewal could be circumvented by fine-tuning the expression of the RNA decay machinery. These results demonstrate that post-transcriptional dynamics dictate the negative effect of aged matrices on MuSC self-renewal.
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http://biorxiv.org/cgi/content/short/2023.02.24.529950v1?rss=1
Authors: Hettinger, Z. R., Hu, S., Mamiya, H., Sahu, A., Iijima, H., Wang, K., Gilmer, G., Miller, A., Nasello, G., D'Amore, A., Vorp, D., Rando, T. A., Xing, J., Ambrosio, F.
Abstract:
Loss of muscle stem cell (MuSC) self-renewal with aging reflects a combination of influences from the intracellular (e.g., post-transcriptional modifications) and extracellular (e.g., matrix stiffness) environment. Whereas conventional single cell analyses have revealed valuable insights into factors contributing to impaired self-renewal with age, most are limited by static measurements that fail to capture nonlinear dynamics. Using bioengineered matrices mimicking the stiffness of young and old muscle, we showed that while young MuSCs were unaffected by aged matrices, old MuSCs were phenotypically rejuvenated by young matrices. Dynamical modeling of RNA velocity vector fields in silico revealed that soft matrices promoted a self-renewing state in old MuSCs by attenuating RNA decay. Vector field perturbations demonstrated that the effects of matrix stiffness on MuSC self-renewal could be circumvented by fine-tuning the expression of the RNA decay machinery. These results demonstrate that post-transcriptional dynamics dictate the negative effect of aged matrices on MuSC self-renewal.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Feb 25, 2023
Format:
Podcast episode
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