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单细胞 RNA-Seq 揭示创伤后骨关节炎免疫景观的变化。

Single-cell RNA-Seq reveals changes in immune landscape in post-traumatic osteoarthritis.

机构信息

Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA, United States.

School of Natural Sciences, University of California Merced, Merced, CA, United States.

出版信息

Front Immunol. 2022 Jul 29;13:938075. doi: 10.3389/fimmu.2022.938075. eCollection 2022.

DOI:10.3389/fimmu.2022.938075
PMID:35967299
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9373730/
Abstract

Osteoarthritis (OA) is the most common joint disease, affecting over 300 million people world-wide. Accumulating evidence attests to the important roles of the immune system in OA pathogenesis. Understanding the role of various immune cells in joint degeneration or joint repair after injury is vital for improving therapeutic strategies for treating OA. Post-traumatic osteoarthritis (PTOA) develops in ~50% of individuals who have experienced an articular trauma like an anterior cruciate ligament (ACL) rupture. Here, using the high resolution of single-cell RNA sequencing, we delineated the temporal dynamics of immune cell accumulation in the mouse knee joint after ACL rupture. Our study identified multiple immune cell types in the joint including neutrophils, monocytes, macrophages, B cells, T cells, NK cells and dendritic cells. Monocytes and macrophage populations showed the most dramatic changes after injury. Further characterization of monocytes and macrophages reveled 9 major subtypes with unique transcriptomics signatures, including a tissue resident Lyve1Folr2 macrophage population and Trem2Fcrls recruited macrophages, both showing enrichment for phagocytic genes and growth factors such as , and We also identified several genes induced or repressed after ACL injury in a cell type-specific manner. This study provides new insight into PTOA-associated changes in the immune microenvironment and highlights macrophage subtypes that may play a role in joint repair after injury.

摘要

骨关节炎（OA）是最常见的关节疾病，影响全球超过 3 亿人。越来越多的证据证明免疫系统在 OA 发病机制中起着重要作用。了解各种免疫细胞在关节退变或受伤后关节修复中的作用，对于改善治疗 OA 的治疗策略至关重要。创伤后骨关节炎（PTOA）发生在约 50%经历过关节创伤（如前交叉韧带（ACL）破裂）的个体中。在这里，我们使用单细胞 RNA 测序的高分辨率，描绘了 ACL 破裂后小鼠膝关节中免疫细胞积累的时间动态。我们的研究在关节中鉴定出多种免疫细胞类型，包括中性粒细胞、单核细胞、巨噬细胞、B 细胞、T 细胞、NK 细胞和树突状细胞。单核细胞和巨噬细胞群体在受伤后表现出最显著的变化。进一步对单核细胞和巨噬细胞进行特征分析揭示了 9 种具有独特转录组学特征的主要亚型，包括组织驻留 Lyve1Folr2 巨噬细胞群和 Trem2Fcrls 募集的巨噬细胞，两者均富含吞噬基因和生长因子，如 、 和 。我们还鉴定了几个在 ACL 损伤后以细胞类型特异性方式诱导或抑制的基因。这项研究为 PTOA 相关的免疫微环境变化提供了新的见解，并强调了可能在受伤后关节修复中发挥作用的巨噬细胞亚型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/44bc8c949c83/fimmu-13-938075-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/9b09c29b2991/fimmu-13-938075-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/d1d25a38fbf1/fimmu-13-938075-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/c5a093d1fccf/fimmu-13-938075-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/964e12d728a4/fimmu-13-938075-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/44bc8c949c83/fimmu-13-938075-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/9b09c29b2991/fimmu-13-938075-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/074ca65a8d98/fimmu-13-938075-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/6edacb58a762/fimmu-13-938075-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/ab33b83f4115/fimmu-13-938075-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/d1d25a38fbf1/fimmu-13-938075-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/c5a093d1fccf/fimmu-13-938075-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/964e12d728a4/fimmu-13-938075-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8956/9373730/44bc8c949c83/fimmu-13-938075-g009.jpg

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