BEST4⁺ cells in the intestinal epithelium.

Area of Science:

• Gastroenterology
• Cell Biology
• Human Physiology

Background:

• Single-cell transcriptomics has identified a novel lineage of mature absorptive cells in the human intestinal epithelium, designated BEST4-positive (BEST4+) cells.
• These cells are characterized by the expression of BEST4 and other markers like OTOP2, CA7, GUCA2A, GUCA2B, and SPIB.
• BEST4+ cells are present throughout the human small and large intestine from early development, constituting less than 5% of epithelial cells.

Purpose of the Study:

• To review and summarize the existing literature on BEST4+ cells in the human intestinal epithelium.
• To describe the predicted roles of BEST4+ cells in intestinal health and disease.
• To highlight the challenges and potential solutions for studying BEST4+ cells due to their absence in mice.

Main Methods:

• Review of current scientific literature on BEST4+ cells.
• Analysis of gene expression profiles from single-cell transcriptomics studies.
• Evaluation of potential animal models and in vitro systems for studying BEST4+ cells.

Main Results:

• BEST4+ cells exhibit location-specific gene expression, suggesting functional specialization in different gut regions (e.g., CFTR expression in the small intestine).
• Predicted functions include sensing/regulating luminal pH, tuning guanylyl cyclase-C signaling, electrolyte transport, mucus hydration, and antimicrobial peptide secretion.
• BEST4+ cells are found in human intestinal organoids and in several animal species (macaque, pig, zebrafish, rabbit), but not in mice.

Conclusions:

• BEST4+ cells represent a distinct absorptive cell subtype with critical roles in intestinal homeostasis.
• Functional validation of their proposed roles requires alternative models like human intestinal organoids or suitable animal models (e.g., rabbits).
• Understanding BEST4+ cells is vital for deciphering intestinal function and disease, especially given their unique characteristics and absence in mice.