Single-cell RNA sequencing unveils the activation of EGR1-ATF3 signaling in EGR1 + muscle stem cells during human paravertebral muscle degeneration

Single-cell RNA sequencing unveils the activation of EGR1-ATF3 signaling in EGR1 + muscle stem cells during human paravertebral muscle degeneration

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Background: Paravertebral muscles (PVM) degeneration (PMD) is closely associated with low back pain.Muscle stem cells (MuSCs) can promote muscle regeneration and repair.However, our 275/60r15 mickey thompson understanding of the cellular composition of PVM and the key genes-mediated MuSCs functions is limited.Methods: We analyzed cells heterogeneity and identified key genes using scRNA-seq.

To validate the presence of EGR1 + MuSCs, we performed Flow cytometry assays.We utilized pseudo-time, CytoTRACE, and RNA velocity to reconstruct cells differentiation trajectory.CellPhoneDB was used to identify the interactions between MuSCs and other cells.Results: We identified 22 cell clusters and 10 cell types, including MuSCs.

We found EGR1 + MuSCs representing the activated subset.We observed the overall number of MuSCs decreased, while the proportion of EGR1 + MuSCs gradually increased during PMD.We demonstrated the target ATF3 of EGR1 and EGR1 were significantly upregulated in PMD, suggesting EGR1-ATF3 signaling may regulate MuSCs functions.Cell differentiation trajectory indicated EGR1 + MuSCs exhibited higher stemness.

We discovered trophy husband apron immune cells, fibroblasts, and endothelial cells may collaborate with MuSCs through specific ligand-receptor pairs to regulate MuSCs functions.Conclusion: These findings unveils the activation of EGR1-ATF3 signaling in EGR1 + MuSCs, providing new insights into the cellular and molecular mechanisms underlying PMD.