Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction

To elucidate the mechanism underlying bone erosion in cholesteatoma, we performed scRNA-seq using human cholesteatoma tissues surgically resected from patients. We focused on pathogenic fibroblasts or keratinocytes, and therefore CD45-negative cells were collected for scRNA-seq analysis to exclude hematopoietic cell lineages. As there are no “normal” tissues in the middle ear that correspond to cholesteatoma, retroauricular skin at the incision site was used as the control for analysis of cholesteatoma. We dentified a characteristic pathogenic fibroblast subset with abundant expression of inhibin ßA. Overall design: Expression profiling by high throughput sequencing