» In this study, we utilize multi-omics technologies to characterize with high throughput and temporal resolution, the molecular and cellular dynamics that underlie skeletal muscle regeneration following acute injury. Using the datasets herein, we characterize for the first time, the temporal chromatin accessibility dynamics that underlies muscle regeneration. Notably, we also identify and characterize for the first time, the self-renewing trajectory that enables the repopulation of muscle stem cells during muscle regeneration. We have made an annotated version of our datasets available for the benefit of the muscle regeneration community and for other scientific communities.
Successful skeletal muscle regeneration is primarily mediated by muscle stem cells or satellite cells which express Pax7. In homeostasis, these satellite cells exist in a ‘genuine quiescent’ state, although some satellite cells may also be primed. After an acute injury, satellite cells, enabled by several other niche cells in the muscle tissue, undergo a series of molecular and cellular changes such as activation, proliferation, and differentiation. These processes culminate in the generation of nascent muscle fibers or the restoration of worn-out muscle fibers, leading to the restoration of muscle function. To prevent the depletion of the quiescent satellite cell pool, some satellite cells must resist the ambient differentiation signals and undergo the self-renewal process. While the differentiation process has been well characterized, little is known about the mechanism of satellite cell self-renewal. Furthermore, the molecular identity of self-renewing satellite cells remains unknown. To fill this gap, we utilize single nuclei ATACseq with high temporal resolution to characterize the temporal dynamics of chromatin accessibility in satellite cells and other muscle niche cells during muscle regeneration. This enables us to identify for the first time the self-renewing trajectory undertaken by satellite cells for their long-term repopulation. We also validated these findings using single-cell RNAseq and other protein-level assays.
A visualization of the snATACseq data for all the identified muscle niche cells have been provided herein for the benefit and exploration of the muscle regeneration and broader scientific community. We have also provided subclustered visualization of immune cells and satellite cells to enable a more resolved expression of the cellular and molecular dynamics of these cell types during muscle regeneration. On the other hand, a visualization of the single-cell RNAseq data that was used to validate our findings has also been provided herein.
» Interactive browser for single cell sequencing
The single cell sequencing database is a single cell RNA-seq and ATAC-seq results report system.