Single Cell Compendium of Muscle Microenvironment in Peripheral Artery Disease Reveals Altered Endothelial Diversity and LYVE1+ Macrophage Activation
About the project:
Peripheral artery disease (PAD) results from atherosclerosis and chronic narrowing of lower limb arteries, leading to decreased muscle perfusion. Current treatments are suboptimal, partly due to limited understanding of PAD muscle pathology. In this study, we used single-cell RNA sequencing and spatial transcriptomics to analyze the composition of the muscle microenvironment in non-ischemic patients and patients with PAD. We identified ATF3/ATF4+ endothelial cells (ECs) that exhibit altered angiogenic and immune regulatory profiles during PAD and confirmed that ATF4 signaling in ECs is required for effective ischemia recovery. In addition, capillary ECs display features of endothelial-to-mesenchymal transition. Furthermore, LYVE1hiMHCIIlow macrophages are the dominant macrophage population in human muscle, adopting a more pro-inflammatory profile during PAD. Finally, we analyzed alterations in intercellular communication within the muscle microenvironment during PAD and confirmed that EC-derived factors can influence macrophage polarization. This dataset deeply characterizes the PAD muscle microenvironment and provides a resource for exploration of targeted therapies.
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Information available on this website:
Full dataset: Visualization of gene expression and cell type information of the complete dataset from human skeletal muscle in TSNE, Dot plots and Violin plots. Including all detected cell types.
Endothelial cells: Reclustering of endothelial cells from the full dataset. Visualization of gene expression and cell type information of EC subtypes from human skeletal muscle in TSNE, Dot plots and Violin plots.
Monocytes/Macrophages: Reclustering of monocytes/macrophages from the full dataset. Visualization of gene expression and cell type information of monocytes/macrophages subtypes from human skeletal muscle in TSNE, Dot plots and Violin plots.
Celastrol bulk RNAseq: Visualization of normalized counts of muscle ECs isolated from PAD patients. Cells were treated in vitro for 24h with Vehicle (DMSO) or celastrol (125nM or 250nM). Full RNAseq data of Vehicle vs 125nM and Vehicle vs 250nM is available to download.
Contact information:
For questions or suggestions about the project, please contact Prof. Dr. Katrien De Bock at katrien-debock@ethz.ch
Website developed and maintained by Guillermo Turiel. For website questions, suggestions or issues, please contact Guillermo Turiel at guillermoturiel@gmail.com
250nM vs Vehicle
125nM vs Vehicle
