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

Sebastian, Aimy; Hum, Nicholas R.; McCool, Jillian L.; Wilson, Stephen P.; Murugesh, Deepa K.; Martin, Kelly A.; Rios-Arce, Naiomy Deliz; Amiri, Beheshta; Christiansen, Blaine A.; Loots, Gabriela G.

doi:10.3389/fimmu.2022.938075

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

Journal Article · Fri Jul 29 00:00:00 EDT 2022 · Frontiers in Immunology

DOI:https://doi.org/10.3389/fimmu.2022.938075· OSTI ID:1879143

Sebastian, Aimy; Hum, Nicholas R.; McCool, Jillian L.; Wilson, Stephen P.; Murugesh, Deepa K.; Martin, Kelly A.; Rios-Arce, Naiomy Deliz; Amiri, Beheshta; Christiansen, Blaine A.; Loots, Gabriela G.

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 Lyve1 ^hi Folr2 ^hi macrophage population and Trem2 ^hi Fcrls ⁺ recruited macrophages, both showing enrichment for phagocytic genes and growth factors such as Igf1 , Pdgfa and Pdgfc. 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.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1879143

Alternate ID(s):: OSTI ID: 2008157

Report Number(s):: LLNL-JRNL-834117; 938075

Journal Information:: Frontiers in Immunology, Journal Name: Frontiers in Immunology Vol. 13; ISSN 1664-3224

Publisher:: Frontiers Media SACopyright Statement

Country of Publication:: Switzerland

Language:: English

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

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