Related Experiment Video
Updated: Mar 16, 2026
Microfluidics-based High-throughput Circulating Tumor Cell Sorting and Single-cell Sequencing Technology
Published on: November 14, 2025
Single-cell RNA sequencing provides insights into the potential cellular origins and microenvironment of Extramammary
Rui Li1, Feifei Ren1, Hongyang Li1
1Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China.
Abstract:
Extramammary Paget's disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential. The exact origin of the tumor is still undefined. To explore potential cellular origin-related signals and depict a relatively comprehensive cellular landscape of EMPD, we collected 50,180 cells from patients with EMPD. We detected a distinct basal keratinocyte cell population characterized by New York Breast-1 (NY-BR-1) expression, which exhibited a transcriptional trajectory toward Paget-like phenotype. We also presented a comprehensive single-cell profile of immune cells and fibroblasts in EMPD. The fibroblasts exhibited a markedly central position in outgoing and incoming signaling interactions. The upregulation of the MK pathway and the downregulation of the MIF pathway in EMPD may promote fibroblast-immune crosstalk and tumor progression. This study provided a novel perspective on potential origin-related transcriptional programs in EMPD and highlighted a global reprogramming of cell-cell communication in EMPD, driven predominantly by fibroblast-derived interactions.
Insights
Extramammary Paget's disease (EMPD) may originate from basal keratinocytes expressing NY-BR-1. Fibroblast-immune cell interactions, influenced by MK and MIF pathways, drive EMPD progression and communication.
Area of Science:
- Oncology
- Dermatology
- Cell Biology
Background:
- Extramammary Paget's disease (EMPD) is a rare, recurring malignancy with metastatic potential.
- The cellular origin of EMPD remains poorly understood, hindering targeted therapies.
Purpose of the Study:
- To investigate the cellular origins and landscape of EMPD.
- To identify key signaling pathways and cell-cell interactions involved in EMPD progression.
Main Methods:
- Single-cell RNA sequencing of 50,180 cells from EMPD patients.
- Analysis of transcriptional trajectories and cell-cell communication networks.
- Identification of key molecular pathways (e.g., MK, MIF).
Main Results:
- A distinct basal keratinocyte population expressing NY-BR-1 was identified, showing a trajectory toward a Paget-like phenotype.
- Fibroblasts play a central role in cell-cell signaling within the EMPD microenvironment.
- Upregulation of the MK pathway and downregulation of the MIF pathway were observed, potentially promoting tumor progression.
Conclusions:
- Basal keratinocytes expressing NY-BR-1 are a potential cellular origin for EMPD.
- Fibroblast-immune cell crosstalk significantly influences EMPD progression.
- Understanding these interactions offers novel therapeutic targets for EMPD.
