Spatiotemporal mapping of immune and stem cell dysregulation after volumetric muscle loss

Spatiotemporal mapping of immune and stem cell dysregulation after volumetric muscle loss(Dataset ID: STDS0000180)

573

719

PMID: 36821376 (IF:8.0 Q1)

Catalog

Dataset information

Contributors

Accessions

Reference way

Dataset information

Summary:

Volumetric muscle loss (VML) is an acute trauma that results in persistent inflammation, supplantation of muscle tissue with fibrotic scarring, and decreased muscle function. The cell types, nature of cellular communication, and tissue locations that drive the aberrant VML response have remained elusive. Herein, we used spatial transcriptomics on mouse and canine models of VML and observed VML engenders a unique spatial pro-fibrotic pattern driven by crosstalk between fibrotic and inflammatory macrophages and mesenchymal derived cells. The dysregulated response was conserved between murine and canine VML models, albeit with varying kinetics, and impinged on muscle stem cell mediated repair. Targeting this circuit in a murine model resulted in increased regeneration and reductions in inflammation and fibrosis. Collectively, these results enhance our understanding of the cellular crosstalk that drives aberrant regeneration and provides further insight into possible avenues for fibrotic therapy exploration.

Overall design:

Spatial gene expression profiling was performed on flash-frozen, OCT embedded muscle tissue from mouse and canine post VML injury. Canine tissues were collected from two animals in different wound locations for a total of three spatial samples. Four replicates were generated for each treatment in mice (vehicle and ITD1) at 7 days post injury, and two replicates were generated for 14 days post injury.

Technology:

10x Visium

Platform:

Illumina NovaSeq 6000, Illumina NovaSeq 6000

Species:

Mus musculus(mm10)

Canis lupus familiaris(canFam3)

Tissues:

Muscle

Organ parts:

Skeletal Muscle

Sex:

F/M

Submission date: 2022-06-08Update date: 2023-02-24

Sample number: 22Section number: 22

Contributors

Aguilar; Carlos Andres; Larouche; Jacqueline A; Wallace; Emily C; Spence; Bonnie D; Johnson; Scott A; Kulkarni; Mangesh; Buras; Eric; Brown; Bryan N; Badylak; Stephen F; Aguilar; Carlos A

Accessions

GEO Series Accessions: GSE205707

Reference way

Citation: Larouche, Jacqueline A et al. “Spatiotemporal mapping of immune and stem cell dysregulation after volumetric muscle loss.” JCI insight vol. 8,7 e162835. 10 Apr. 2023, doi:10.1172/jci.insight.162835