Single-Cell RNA Sequencing Unifies Developmental Programs of Esophageal and Gastric Intestinal Metaplasia

Area of Science:

• Gastroenterology and Molecular Biology
• Cancer Precursor Research
• Single-cell Genomics

Background:

• Intestinal metaplasia in the esophagus (BE-IM) and stomach (GIM) are precursors to adenocarcinoma.
• These conditions are thought to arise from distinct inflammatory triggers.
• Understanding their shared or divergent development is crucial for cancer prevention.

Purpose of the Study:

• To investigate the molecular and developmental similarities between BE-IM and GIM.
• To construct a comprehensive atlas of the gastrointestinal tract in health and disease.
• To identify potential common pathways for detection and treatment.

Main Methods:

• Single-cell RNA sequencing of the entire gastrointestinal tract.
• Protein expression studies.
• Analysis of normal, metaplastic, and atrophic gastritis tissues.

Main Results:

• BE-IM and GIM exhibit shared molecular features and phenotypic mosaicism, with cells showing both gastric and intestinal properties.
• Esophageal gastric metaplasia (E-GM) transcriptionally resembles atrophic gastritis and has a lower mutational burden than BE-IM.
• Both GIM and BE-IM are associated with a protumorigenic, activated fibroblast microenvironment.

Conclusions:

• BE-IM and GIM can be viewed as molecularly similar entities in adjacent organs.
• These findings support the development of shared detection and treatment strategies for BE-IM and GIM.
• The study highlights a common developmental trajectory for these precancerous lesions.