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Article

Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes

1
Lawrence Livermore National Laboratory, Physical and Life Science Directorate, Livermore, CA 94550, USA
2
School of Natural Sciences, University of California Merced, Merced, CA 95343, USA
3
Department of Orthopaedic Surgery, University of California Davis Health, Sacramento, CA 95817, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Gundula Schulze-Tanzil
Cells 2021, 10(6), 1462; https://doi.org/10.3390/cells10061462
Received: 5 May 2021 / Revised: 2 June 2021 / Accepted: 7 June 2021 / Published: 10 June 2021
(This article belongs to the Special Issue Cell and Molecular Causes of Joint Inflammation and Damage)
Articular cartilage is a connective tissue lining the surfaces of synovial joints. When the cartilage severely wears down, it leads to osteoarthritis (OA), a debilitating disease that affects millions of people globally. The articular cartilage is composed of a dense extracellular matrix (ECM) with a sparse distribution of chondrocytes with varying morphology and potentially different functions. Elucidating the molecular and functional profiles of various chondrocyte subtypes and understanding the interplay between these chondrocyte subtypes and other cell types in the joint will greatly expand our understanding of joint biology and OA pathology. Although recent advances in high-throughput OMICS technologies have enabled molecular-level characterization of tissues and organs at an unprecedented resolution, thorough molecular profiling of articular chondrocytes has not yet been undertaken, which may be in part due to the technical difficulties in isolating chondrocytes from dense cartilage ECM. In this study, we profiled articular cartilage from healthy and injured mouse knee joints at a single-cell resolution and identified nine chondrocyte subtypes with distinct molecular profiles and injury-induced early molecular changes in these chondrocytes. We also compared mouse chondrocyte subpopulations to human chondrocytes and evaluated the extent of molecular similarity between mice and humans. This work expands our view of chondrocyte heterogeneity and rapid molecular changes in chondrocyte populations in response to joint trauma and highlights potential mechanisms that trigger cartilage degeneration. View Full-Text
Keywords: osteoarthritis; chondrocyte heterogeneity; scRNA-seq; PTOA; cartilage; gene expression; knee injury osteoarthritis; chondrocyte heterogeneity; scRNA-seq; PTOA; cartilage; gene expression; knee injury
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MDPI and ACS Style

Sebastian, A.; McCool, J.L.; Hum, N.R.; Murugesh, D.K.; Wilson, S.P.; Christiansen, B.A.; Loots, G.G. Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes. Cells 2021, 10, 1462. https://doi.org/10.3390/cells10061462

AMA Style

Sebastian A, McCool JL, Hum NR, Murugesh DK, Wilson SP, Christiansen BA, Loots GG. Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes. Cells. 2021; 10(6):1462. https://doi.org/10.3390/cells10061462

Chicago/Turabian Style

Sebastian, Aimy, Jillian L. McCool, Nicholas R. Hum, Deepa K. Murugesh, Stephen P. Wilson, Blaine A. Christiansen, and Gabriela G. Loots. 2021. "Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes" Cells 10, no. 6: 1462. https://doi.org/10.3390/cells10061462

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