Single-cell dissection of cellular and molecular features underlying human cervical squamous cell carcinoma initiation and progression.

Cervical squamous cell carcinoma (CESC) is a prototypical human cancer with well-characterized pathological stages of initiation and progression. However, high-resolution knowledge of the transcriptional programs underlying each stage of CESC is lacking, and important questions remain. We performed single-cell RNA sequencing of 76,911 individual cells from 13 samples of human cervical tissues at various stages of malignancy, illuminating the transcriptional tumorigenic trajectory of cervical epithelial cells and revealing key factors involved in CESC initiation and progression. In addition, we found significant correlations between the abundance of specific myeloid, lymphoid, and endothelial cell populations and the progression of CESC, which were also associated with patients' prognosis. Last, we demonstrated the tumor-promoting function of matrix cancer-associated fibroblasts via the NRG1-ERBB3 pathway in CESC. This study provides a valuable resource and deeper insights into CESC initiation and progression, which is helpful in refining CESC diagnosis and for the design of optimal treatment strategies.