Single-cell analysis identifies dysregulated cell type-specific gene programs and intercellular crosstalk underlying...

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Colorectal cancer is a major cause of cancer mortality.
• The adenoma-carcinoma sequence describes tumor progression, but cell-specific gene programs driving malignancy are unclear.
• Tumor microenvironment interactions are critical but poorly understood.

Purpose of the Study:

• To analyze cell type-specific gene expression in colorectal carcinoma.
• To investigate intercellular communication between cancer cells and the tumor microenvironment.
• To identify key regulators and molecular mechanisms in colorectal tumorigenesis.

Main Methods:

• Single-nucleus RNA sequencing of colorectal carcinoma and matched normal tissues.
• Analysis of gene expression modules, transcription factor activity, and intercellular communication networks.
• Functional assessment of tumor microenvironment components.

Main Results:

• Dysregulated gene programs identified in individual cell types within colorectal tumors.
• Activated stemness modules and repressed apoptosis/inflammatory signaling in epithelial cells.
• Key transcription factors CEBPB, RUNX1, FOXP1, and POU5F1 showed altered activity.
• Disrupted epithelial-stromal and immune cell crosstalk observed.
• Stromal fibroblasts remodeled extracellular matrix; B-cell immunity was impaired.

Conclusions:

• Single-nucleus analysis reveals cell-specific molecular alterations in colorectal cancer.
• Disrupted intercellular communication and tumor microenvironment reprogramming contribute to tumorigenesis.
• Findings offer insights into colorectal cancer mechanisms and potential therapeutic targets.