| Description |
Intrauterine adhesion (IUA), is a common acquired endometrial disease, which is mainly secondary to endometrial injury, resulting in severe implications for women's reproductive health, causing years of potential infertility or recurrent pregnancy loss. However, the underlying molecular and cellular mechanisms that drive this pathophysiology remain largely unknown, thereby hindering early diagnosis and treatment. Here, we aimed to address this knowledge gap by profiling integrated single-cell transcriptomes of over 39,000 individual cells derived from both IUA and normal endometrial tissues. We identified distinct changes in cell type-specific and molecular signatures associated with IUA, including the inflammatory activation in immune cells, diffuse damage in epithelial subpopulations and the deposition of collagen secreted by fibroblasts subpopulations. Furthermore, we revealed a specific subpopulation of macrophages, marked by the expression of TREM2, was activated with pro-inflammatory properties in IUA, regulated by multiple transcription factors and involved in the multiple signaling pathway, such as p38MAPK cascade and steroid hormone response. Interestingly, we observed that ANXA1+ NK cell subpopulations were particularly vulnerable, exhibiting decreased cell density and the highest number of differentially expressed genes which involved in the wound healing signaling pathway. Moreover, we identified two distinct unciliated epithelial subtypes characterized by the expression of MMP7 and CCL5, respectively. These subpopulations were the most susceptible subpopulations to epithelial injury, which may provide potential targets for the diagnostics and treatment. Collectively, our study provides an integrated view of the IUA microenvironment, serving as a comprehensive cell atlas of the disease in affected individuals. The insights gained from this study provide valuable resources for future diagnostics and treatment. |
