AI Article Synopsis
- Single-cell transcriptomics provide a detailed analysis of various segments of the human intestine, revealing 25 distinct epithelial lineage clusters.
- Differences in expression of stem cell markers and receptors indicate that traditional understanding of certain cell types, like Paneth cells, may need revision.
- The findings highlight significant regional variations in gene expression related to nutrient absorption and immune interaction, offering insights into potential responses to environmental factors and medications in the gut.
Article Abstract
Background & Aims: Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies analyzing healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon from 3 human beings.
Methods: A total of 12,590 single epithelial cells from 3 independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and their capacity for response to extrinsic signals along the gut axis across different human beings.
Results: Cells were assigned to 25 epithelial lineage clusters. Multiple accepted intestinal stem cell markers do not specifically mark all human intestinal stem cells. Lysozyme expression is not unique to human Paneth cells, and Paneth cells lack expression of expected niche factors. Bestrophin 4 (BEST4) cells express Neuropeptide Y (NPY) and show maturational differences between the small intestine and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell junctions, and nutrient absorption genes show unappreciated regional expression differences across lineages. The differential expression of receptors and drug targets across lineages show biological variation and the potential for variegated responses.
Conclusions: Our study identifies novel lineage marker genes, covers regional differences, shows important differences between mouse and human gut epithelium, and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves likely functional differences across anatomic regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043569 | PMC |
| http://dx.doi.org/10.1016/j.jcmgh.2022.02.007 | DOI Listing |
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