Infant and Adult Human Intestinal Enteroids are Morphologically and Functionally Distinct

Area of Science:

• Gastroenterology
• Developmental Biology
• Cell Biology

Background:

• Human intestinal enteroids (HIEs) are crucial models for studying the intestinal epithelium.
• Infant HIEs are underrepresented in research despite significant developmental changes during infancy.

Approach:

• Established jejunal HIEs from infant surgical samples.
• Compared infant and adult HIEs using RNA sequencing (RNA-Seq) and morphologic analyses.
• Validated transcriptomic differences with functional studies.

Key Points:

• Infant and adult HIEs exhibit distinct transcriptomes, differing in cell differentiation, proliferation, lipid metabolism, innate immunity, and adhesion pathways.
• Infant HIEs show higher proportions of enterocytes, goblet cells, and enteroendocrine cells, with more proliferative cells in undifferentiated cultures.
• Infant HIEs display immature gastrointestinal features: shorter cell height, reduced barrier integrity, and weaker innate immune responses.

Conclusions:

• Infant HIEs accurately model the infant gut epithelium and its unique characteristics.
• Infant HIEs serve as a valuable ex-vivo model for infant-specific disease research and drug discovery.