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Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse

Transplant rejection remains a major barrier to graft survival and involves a diversity of cell types. However, the heterogeneity of each cell type in the allograft remains poorly defined. In the present study, we used single-cell RNA sequencing technology to analyze graft-infiltrating cells to desc...

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Autores principales: Tang, Yunhua, Wang, Jiali, Zhang, Yixi, Li, Jun, Chen, Maogen, Gao, Yifang, Dai, Meiqin, Lin, Shengjie, He, Xiaoshun, Wu, Chenglin, Shi, Xiaomin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866760/
https://www.ncbi.nlm.nih.gov/pubmed/35222420
http://dx.doi.org/10.3389/fimmu.2022.832573
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author Tang, Yunhua
Wang, Jiali
Zhang, Yixi
Li, Jun
Chen, Maogen
Gao, Yifang
Dai, Meiqin
Lin, Shengjie
He, Xiaoshun
Wu, Chenglin
Shi, Xiaomin
author_facet Tang, Yunhua
Wang, Jiali
Zhang, Yixi
Li, Jun
Chen, Maogen
Gao, Yifang
Dai, Meiqin
Lin, Shengjie
He, Xiaoshun
Wu, Chenglin
Shi, Xiaomin
author_sort Tang, Yunhua
collection PubMed
description Transplant rejection remains a major barrier to graft survival and involves a diversity of cell types. However, the heterogeneity of each cell type in the allograft remains poorly defined. In the present study, we used single-cell RNA sequencing technology to analyze graft-infiltrating cells to describe cell types and states associated with acute rejection in a mouse heart transplant model. Unsupervised clustering analysis revealed 21 distinct cell populations. Macrophages formed five cell clusters: two resident macrophage groups, two infiltrating macrophage groups and one dendritic cell-like monocyte group. Infiltrating macrophages were predominantly from allogeneic grafts. Nevertheless, only one infiltrating macrophage cluster was in an active state with the upregulation of CD40, Fam26f and Pira2, while the other was metabolically silent. Re-clustering of endothelial cells identified five subclusters. Interestingly, one of the endothelial cell populations was almost exclusively from allogeneic grafts. Further analysis of this population showed activation of antigen processing and presentation pathway and upregulation of MHC class II molecules. In addition, Ubiquitin D was specifically expressed in such endothelial cell population. The upregulation of Ubiquitin D in rejection was validated by staining of mouse heart grafts and human kidney biopsy specimens. Our findings present a comprehensive analysis of intra-graft cell heterogeneity, describe specific macrophage and endothelial cell populations which mediate rejection, and provide a potential predictive biomarker for rejection in the clinic.
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spelling pubmed-88667602022-02-25 Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse Tang, Yunhua Wang, Jiali Zhang, Yixi Li, Jun Chen, Maogen Gao, Yifang Dai, Meiqin Lin, Shengjie He, Xiaoshun Wu, Chenglin Shi, Xiaomin Front Immunol Immunology Transplant rejection remains a major barrier to graft survival and involves a diversity of cell types. However, the heterogeneity of each cell type in the allograft remains poorly defined. In the present study, we used single-cell RNA sequencing technology to analyze graft-infiltrating cells to describe cell types and states associated with acute rejection in a mouse heart transplant model. Unsupervised clustering analysis revealed 21 distinct cell populations. Macrophages formed five cell clusters: two resident macrophage groups, two infiltrating macrophage groups and one dendritic cell-like monocyte group. Infiltrating macrophages were predominantly from allogeneic grafts. Nevertheless, only one infiltrating macrophage cluster was in an active state with the upregulation of CD40, Fam26f and Pira2, while the other was metabolically silent. Re-clustering of endothelial cells identified five subclusters. Interestingly, one of the endothelial cell populations was almost exclusively from allogeneic grafts. Further analysis of this population showed activation of antigen processing and presentation pathway and upregulation of MHC class II molecules. In addition, Ubiquitin D was specifically expressed in such endothelial cell population. The upregulation of Ubiquitin D in rejection was validated by staining of mouse heart grafts and human kidney biopsy specimens. Our findings present a comprehensive analysis of intra-graft cell heterogeneity, describe specific macrophage and endothelial cell populations which mediate rejection, and provide a potential predictive biomarker for rejection in the clinic. Frontiers Media S.A. 2022-02-10 /pmc/articles/PMC8866760/ /pubmed/35222420 http://dx.doi.org/10.3389/fimmu.2022.832573 Text en Copyright © 2022 Tang, Wang, Zhang, Li, Chen, Gao, Dai, Lin, He, Wu and Shi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Tang, Yunhua
Wang, Jiali
Zhang, Yixi
Li, Jun
Chen, Maogen
Gao, Yifang
Dai, Meiqin
Lin, Shengjie
He, Xiaoshun
Wu, Chenglin
Shi, Xiaomin
Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse
title Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse
title_full Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse
title_fullStr Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse
title_full_unstemmed Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse
title_short Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse
title_sort single-cell rna sequencing identifies intra-graft population heterogeneity in acute heart allograft rejection in mouse
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866760/
https://www.ncbi.nlm.nih.gov/pubmed/35222420
http://dx.doi.org/10.3389/fimmu.2022.832573
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