Spatial and single-cell transcriptomics landscape of adenomyosis

Adenomyosis is a prevalent and non-cancerous uterine disease which can significantly impaired the fertility of reproductive-age women. However, the etiology, as well as the cellular and molecular mechanism underlying adenomyosis remain largely unknown. Here, we utilized cutting-edge spatial and single-cell RNA sequencing technologies to create a comprehensive transcriptional atlas of adenomyosis pathology. Our spatial profiling clearly distinguished gland, mesenchyma and myometrium regions, recapitulating spatial transcriptome structural characteristics of uterus. Moreover, we analyzed the expression profiles of 69,115 single cells and integrated them with spatial data. The analysis of immune cells showed a distinct immune inflammatory microenvironment in the eutopic and ectopic endometrial glands of adenomyosis. Notably, we discovered an increased number of DNAH9 ⁺ ciliated cells in ectopic endometrial glands, indicating their potential role in the formation of ectopic endometrium. These findings provide cellular evidence to support the invagination theory and offer a new vision on the pathophysiology and clinical intervention of adenomyosis.