The Integrated Stress Response Pathway Improves Aged Murine Muscle Stem Cell Activation and in vivo Regeneration.
Brown, A. D.; Scaramozza, A.; Zhang, H.; Mahin, S.; Suresh, N.; Tsusaka, T.; Eliazer, S.; Liu, X.; Feeley, B.; Brack, A. S.
Show abstract
For efficient regeneration, muscle stem cells (MuSCs) transition out of quiescence through a series of progressively more activated states. During MuSC aging, transition through the earliest steps is the slowest and delayed, with the molecular regulators that govern this transition not well characterized. By analyzing the dynamic changes of MuSCs at the molecular (scRNA-Seq and Cell Painting) and phenotypic (heteromotility) level at single cell resolution we found that the Integrated Stress Response (ISR) Pathway is a critical regulator of MuSC transition states. Aged MuSCs have increased baseline ISR activity in quiescence that does not increase during activation to levels observed in adult MuSCs. Rapid and transient pharmacological ISR activation in vitro was sufficient to increase aged MuSC activation rate and migratory behavior as well as alter the transcriptional states toward a younger phenotype. ISR activation also improved aged MuSC potency and aged mouse muscle regeneration in vivo. Therefore, pharmacological activation of the ISR has therapeutic potential to improve MuSC function and skeletal muscle repair during aging.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The immune landscape of murine skeletal muscle regeneration and aging 96%
- Heterogeneity of satellite cells implicates DELTA1/ NOTCH2 signaling in self-renewal 95%
- Single-cell analysis of the muscle stem cell hierarchy identifies heterotypic communication signals involved in skeletal muscle regeneration 95%
Similar papers in this journal
- Fasting Induces a Highly Resilient Deep Quiescent State in Muscle Stem Cells via Ketone Body Signaling 97%
- Muscle-secreted neurturin couples myofiber oxidative metabolism and slow motor neuron identity. 95%
- Mitochondrial Calcium Uptake Declines during Aging and is Directly Activated by Oleuropein to Boost Energy Metabolism and Skeletal Muscle Performance 95%
Similar papers in this journal
- Single Cell Deconstruction of Muscle Stem Cell Heterogeneity During Aging Reveals Sensitivity to the Neuromuscular Junction 97%
- Aging impairs cold-induced beige adipogenesis and adipocyte metabolic reprogramming 95%
- A cell cycle-linked mechanism for the glutamine driven establishment of stem cell fate 95%
Similar papers in this journal
- Muscle regeneration can be rescued in a telomerase deficient zebrafish model of ageing by MMP inhibition 95%
- Single-cell RNA sequencing identifies accumulation of Fcgr2b+ virtual memory like CD8 T cells with cytotoxic and inflammatory potential in aged mouse white adipose tissue 95%
- Senescent cells enhance newt limb regeneration by promoting muscle dedifferentiation 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.