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

被引:34
作者
Burclaff, Joseph [1 ,2 ]
Bliton, R. Jarrett [3 ]
Breau, Keith A. [4 ]
Ok, Meryem T. [3 ]
Gomez-Martinez, Ismael [4 ]
Ranek, Jolene S. [5 ]
Bhatt, Aadra P. [1 ,2 ,6 ]
Purvis, Jeremy E. [5 ,7 ]
Woosley, John T. [8 ]
Magness, Scott T. [1 ,2 ,3 ,4 ,6 ]
机构
[1] Univ North Carolina Chapel Hill North Carolina St, Dept Med, Chapel Hill, NC USA
[2] Univ North Carolina Chapel Hill North Carolina St, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC USA
[3] Univ North Carolina Chapel Hill North Carolina St, Joint Dept Biomed Engn, Chapel Hill, NC USA
[4] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27515 USA
[5] Univ N Carolina, Curriculum Bioinformat & Computat Biol, Chapel Hill, NC 27515 USA
[6] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA
[7] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA
[8] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA
来源
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY | 2022年 / 13卷 / 05期
基金
美国国家卫生研究院;
关键词
scRNAseq; Cell Atlas; Intestinal Stem Cell; Paneth Cell; BEST4; FOLLICLE-ASSOCIATED EPITHELIUM; STEM-CELLS; ENTEROENDOCRINE CELLS; PEYERS PATCH; TUFT CELLS; IMMUNE-RESPONSES; NEUROPEPTIDE-Y; GOBLET CELLS; SELF-RENEWAL; EXPRESSION;
D O I
10.1016/j.jcmgh.2022.02.007
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:1554 / 1589
页数:36
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