A single-cell transcriptional atlas identifies extensive heterogeneity in the cellular composition of tendons

Tendon is a dense, hypocellular connective tissue that transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of tissue homeostasis and disease, but little is known about the diversity of cells that populate tendon. Our objective was to explore the heterogeneity of cells in mouse Achilles tendons using single-cell RNA sequencing. We identified 13 unique cell types in tendons, including 4 previously undescribed populations of fibroblasts. Using pseudotime trajectory machine learning analysis, we provide additional support for the notion that pericytes serve as a progenitor cell population for the fibroblasts that compose adult tendons. These findings identify notable heterogeneity between and within tendon cell populations. This heterogeneity may have important implications for our understanding of how the tendon extracellular matrix is assembled and maintained, and for the design of therapies to treat tendinopathies.