INTEGRATIVE SCRNA-SEQ ANALYSES OF HUMAN ARTICULAR CARTILAGE AND MENISCUS REVEAL A PATHOGENIC, SENESCENT SUBPOPULATION THAT IS EXPANDED IN OSTEOARTHRITIS, SHARED BETWEEN BOTH TISSUES, AND HAS CRITICAL ROLES IN EXTRACELLULAR MATRIX PROPERTIES AND TENASCIN SIGNALING

Abstract

Purpose: RNA-sequencing studies in human osteoarthritis (OA) knees revealed dysregulation of genes involved in extracellular matrix (ECM) properties, circadian rhythm pathways and mechanotransduction. Although useful for a broad view of disease impact, bulk ‘omics technologies only reveal average changes across tissues that are often highly heterogeneous in cell-type composition. Disease-related changes restricted to certain cell subpopulations would be masked. Single-cell RNA sequencing (scRNA-seq) technologies overcome these limitations by capturing global gene expression profiles at a single-cell resolution.