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Status |
Public on Feb 23, 2023 |
Title |
Spatiotemporal mapping of immune and stem cell dysregulation after volumetric muscle loss |
Organisms |
Canis lupus familiaris; Mus musculus |
Experiment type |
Other
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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.
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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.
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Web link |
https://doi.org/10.1172/jci.insight.162835
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Contributor(s) |
Larouche JA, Wallace EC, Spence BD, Johnson SA, Kulkarni M, Buras E, Brown BN, Badylak SF, Aguilar CA |
Citation missing |
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Submission date |
Jun 08, 2022 |
Last update date |
Feb 24, 2023 |
Contact name |
Carlos Andres Aguilar |
E-mail(s) |
caguilar@umich.edu
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Phone |
734-764-8557
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Organization name |
University of Michigan
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Department |
Biomedical Engineering
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Lab |
2100 Gerstacker Bldg
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Street address |
2200 Bonisteel Blvd
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City |
Ann Arbor |
State/province |
MI |
ZIP/Postal code |
48109 |
Country |
USA |
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Platforms (2) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
GPL25760 |
Illumina NovaSeq 6000 (Canis lupus familiaris) |
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Samples (18)
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Relations |
BioProject |
PRJNA847234 |
Supplementary file |
Size |
Download |
File type/resource |
GSE205707_Canis_ST_list.RDS.gz |
737.0 Mb |
(ftp)(http) |
RDS |
GSE205707_Integrated_Merged_spGEX_SeuratObj_v3.RDS.gz |
2.0 Gb |
(ftp)(http) |
RDS |
GSE205707_Mus_ST_list_label_transfer.RDS.gz |
363.4 Mb |
(ftp)(http) |
RDS |
GSE205707_Mus_ST_list_label_transfer_1201.RDS.gz |
441.6 Mb |
(ftp)(http) |
RDS |
GSE205707_RAW.tar |
20.3 Gb |
(http)(custom) |
TAR (of JSON, TIFF) |
GSE205707_canis_merged_414T_415T_425T_426T.RDS.gz |
342.5 Mb |
(ftp)(http) |
RDS |
GSE205707_canis_merged_D0_D7_D14.RDS.gz |
698.5 Mb |
(ftp)(http) |
RDS |
GSE205707_merged_D7_D14.RDS.gz |
234.6 Mb |
(ftp)(http) |
RDS |
GSE205707_merged_filtered_599L_599R_600L_600R_1197L_1203L_1203R_1202L.RDS.gz |
911.5 Mb |
(ftp)(http) |
RDS |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
Processed data provided as supplementary file |