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Cited by 242Single-cell and spatial transcriptomicsDigestive system and related healthIL-33, ST2, and ILC Pathways

A Proximal-to-Distal Survey of Healthy Adult Human Small Intestine and Colon Epithelium by Single-Cell Transcriptomics

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Burclaff, Joseph, Bliton, R. Jarrett, Breau, Keith A., Ok, Meryem T., Gomez-Martinez, Ismael, Ranek, Jolene S., Bhatt, Aadra P., Purvis, Jeremy E. +2 more·2022·Cellular and Molecular Gastroenterology and Hepatology
DOI 10.1016/j.jcmgh.2022.02.007PMC PMC9043569

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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 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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  • Time-resolved scRNA-seq on a KRAS G12D PDO treated with MRTX1133 and cetuximab showed a gradual increase in Paneth-like gene module activity over time, supporting a stepwise transition during treatment.

    “We scored the CRC PDO cells for the published Paneth-like state signatures38,39 and observed a gradual increase in Paneth-like gene module activity over time (Figure S1P), supporting a stepwise transition during treatment.”

    From Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer (2026) · cites this paper as [39]

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Authors
Burclaff, J., Bliton, R. J., Breau, K. A., Ok, M. T., Gomez-Martinez, I., Ranek, J. S., Bhatt, A. P., Purvis, J. E., Woosley, J. T., & Magness, S. T.
Affiliations
University of North Carolina at Chapel Hill (US)
Corresponding author
Magness, Scott T.
ORCID
Venue
Cellular and Molecular Gastroenterology and Hepatology
Publisher
Elsevier BV
Published
2022
Volume
13
Issue
5
Pages
1554-1589
ISSN
2352-345X (ISSN-L)
DOI
10.1016/j.jcmgh.2022.02.007
PMC
PMC9043569
OpenAlex
W4220828290
Cited by
242
References
179
Citations by year
2026: 51 · 2025: 66 · 2024: 59 · 2023: 43 · 2022: 23
FWCI
15.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Gastroenterology and Hepatology (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
UNC-Chapel Hill
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords
intestinal epithelium, small intestine, colon, single-cell transcriptomics, cell atlas, duodenum, jejunum, ileum, ascending colon, transverse colon, descending colon, lineage markers, tuft cells, neuropeptide Y, mucin, nutrient absorption, gut-immune interaction, therapeutic target
MeSH terms
Animals, Colon, Epithelium, Humans, Intestinal Mucosa, Intestine, Small, Mice, Transcriptome

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