Transcriptomic Signatures in Lung Allografts and Their Therapeutic Implications

Figures

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  Figure 1. Coupling ex vivo perfusion systems with transcriptomic analysis. (A) Schematic illustration of proposed setup coupling ex vivo perfusion systems with transcriptomic technology like scRNAseq. The donor lungs are placed on EVLP for subsequent transcriptomic analysis. Numbers in scRNAseq graph represent different cell type clusters. (B) The downstream analysis produces gene expression profiles that can be compared to atlas databanks. (C) Subsequent pathway analysis informs individualized therapeutic strategies to repair and enhance organ function.

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  Figure 2. Pathway interpretation of genes and pathways in current literature. Findings were compiled across various literatures sources and stratified based on changes seen in lungs on EVLP, directly transplanted, or both. Up arrows indicate gene expression were upregulated while down arrows represent gene expression was down regulated.

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  Figure 3. Therapeutic interventions for donor lungs on EVLP. (A) Schematic illustration of physical therapies. At the physical level, mechanical properties inherent to the EVLP circuit may be altered to improve donor lung function. (B) Schematic illustration of pharmacologic therapies. Pharmacologic treatments can be delivered intratracheally or intravascularly to target specific tissue compartments. (C) Schematic illustration of cellular and molecular therapies. Cellular and molecular therapies can be deployed to alter global inflammatory pathways. (D) Finally, gene therapy is the next phase in targeted therapeutics that can reengineer the donor lung for improved performance. Schematic illustration of repressor gene circuit OFF or ON with stimuli that can make a protein of interest. Additionally, CRISPR modifiers are shown with various molecular functions. AM, alveolar macrophage; N, neutrophil; M, monocyte; ATI, alveolar type I cell; ATII, alveolar type II cell; EC, endothelial cell.