(359) Single Cell Transcriptomic Analysis of Acute Heart Rejection in a Rat Model
Heart transplantation (tx) is the last treatment option for end-stage cardiac failure. Acute rejection is among the most common reasons for death after heart transplantation. It also increases the risk for late allograft failure, indicating permanent changes in immune environment of the allograft. I...
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| Published in: | The Journal of heart and lung transplantation Vol. 42; no. 4; pp. S170 - S171 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Elsevier Inc
01-04-2023
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| Online Access: | Get full text |
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| Summary: | Heart transplantation (tx) is the last treatment option for end-stage cardiac failure. Acute rejection is among the most common reasons for death after heart transplantation. It also increases the risk for late allograft failure, indicating permanent changes in immune environment of the allograft. In order to improve survival after transplantation, precise understanding of the cellular and molecular mechanisms is critical. The structural cells of organs are essential partners of immune response, but how the structural cells of the heart participate in the immune response in rejection is poorly understood. In this study, we unravel the single cell landscape of acute rejection in a rat model to describe the transcriptomic changes in both immune and structural heart cell populations.
We performed single nuclei sequencing from heterotopically transplanted rat hearts. The hearts were harvested three and five days after tx and stored in -80°C freezer until sequencing. Samples were lysed and nuclei isolated using filtering techniques and FACS. Samples were sequenced and raw reads were processed using CellRanger. All main data analysis steps were performed using Seurat.
We identified altogether 28 cell clusters including 7 stromal, 5 endothelial, 3 cardiomyocyte, 7 myeloid, 5 lymphoid and one neural cell cluster. In allogenic rejection, there was a marked recruitment of both myeloid and lymphoid immune cells. In addition, changes in cell proportions were observed in one cardiomyocyte cluster as well as in endothelial cell clusters.
In structural cells, differential state analysis revealed transcriptomic changes specific to allogenic rejection. In both fibroblasts and cardiomyocytes, we found increased expression of Serpine1, which regulates wound healing and tissue fibrosis. In the pathway analysis, endothelial cells showed upregulation of collagen synthesis, protein digestion and absorption, cell adhesion and growth. Affected cardiomyocyte pathways were related to altered muscle contractility and ATP metabolism.
Acute rejection changes the cellular composition of the heart muscle dramatically, inducing recruitment of innate and adaptive immune cells and transcriptomic changes in the structural cells of the heart and activating pathways related to immune response, wound healing and cell signaling. Our data provides new insight into rejection and describes pathological changes in structural cells of the heart. |
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| ISSN: | 1053-2498 1557-3117 |
| DOI: | 10.1016/j.healun.2023.02.1663 |