A Single-Cell Atlas of Transcriptome Changes in the Intestinal Epithelium at the Suckling-to-Weaning Transition in...

Area of Science:

• Gastroenterology
• Developmental Biology
• Genomics

Background:

• The dietary transition from suckling to weaning is critical for intestinal development.
• Understanding cellular responses during this period is key to comprehending gut maturation.

Purpose of the Study:

• To identify cell-specific transcriptome alterations in the intestinal epithelium upon solid food ingestion.
• To establish a single-cell atlas of the rabbit intestinal epithelium during the suckling-to-weaning transition.

Main Methods:

• Single-cell RNA sequencing of rabbit cecal epithelial cells from suckling and weaned littermates.
• Comparative transcriptome analysis to identify gene expression changes in distinct cell types.

Main Results:

• Generated the first single-cell atlas of the rabbit intestinal epithelium, highlighting BEST4+ cells.
• Observed extensive, cell-type-specific transcriptome changes, particularly in absorptive and BEST4+ cells.
• Identified remodeling of epithelial defense systems and nutrient handling pathways, alongside changes in microbiota composition.

Conclusions:

• Solid food ingestion profoundly impacts intestinal epithelial cell transcriptomes in a cell-specific manner.
• The rabbit serves as a valuable model for studying intestinal development, including BEST4+ cell function.
• Dietary transition-induced changes are linked to microbiota shifts and can be partially mimicked by butyrate.