Organization of the human intestine at single-cell resolution

The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health 1 . The intesting has a length of over nine metres, along which there are differences in structure...

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Vydané v:	Nature (London) Ročník 619; číslo 7970; s. 572 - 584
Hlavní autori:	Hickey, John W., Becker, Winston R., Nevins, Stephanie A., Horning, Aaron, Perez, Almudena Espin, Zhu, Chenchen, Zhu, Bokai, Wei, Bei, Chiu, Roxanne, Chen, Derek C., Cotter, Daniel L., Esplin, Edward D., Weimer, Annika K., Caraccio, Chiara, Venkataraaman, Vishal, Schürch, Christian M., Black, Sarah, Brbić, Maria, Cao, Kaidi, Chen, Shuxiao, Zhang, Weiruo, Monte, Emma, Zhang, Nancy R., Ma, Zongming, Leskovec, Jure, Zhang, Zhengyan, Lin, Shin, Longacre, Teri, Plevritis, Sylvia K., Lin, Yiing, Nolan, Garry P., Greenleaf, William J., Snyder, Michael
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 20.07.2023 Nature Publishing Group
Predmet:	13 13/1 14 14/63 38/39 38/90 38/91 45 631/208/191 631/208/200 631/553/2694 631/553/2706 Body mass index Cell Differentiation - genetics Cells Chromatin Chromatin - genetics Colon Complexity Composition Epithelial Cells - cytology Epithelial Cells - metabolism Gene Expression Regulation Heritability Humanities and Social Sciences Humans Immunology Immunosurveillance Intestinal Mucosa - cytology Intestine Intestines - cytology Intestines - immunology Large intestine Localization Lymphocytes Microbiota multidisciplinary Neighborhoods Nutrients Science Science (multidisciplinary) Single-Cell Analysis Single-Cell Gene Expression Analysis Small intestine Smooth muscle
ISSN:	0028-0836, 1476-4687, 1476-4687
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Shrnutí:	The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health 1 . The intesting has a length of over nine metres, along which there are differences in structure and function 2 . The localization of individual cell types, cell type development trajectories and detailed cell transcriptional programs probably drive these differences in function. Here, to better understand these differences, we evaluated the organization of single cells using multiplexed imaging and single-nucleus RNA and open chromatin assays across eight different intestinal sites from nine donors. Through systematic analyses, we find cell compositions that differ substantially across regions of the intestine and demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighbourhoods and communities, highlighting distinct immunological niches that are present in the intestine. We also map gene regulatory differences in these cells that are suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation and organization for this organ, and serve as an important reference map for understanding human biology and disease. Intestinal cell types are organized into distinct neighbourhoods and communities within the healthy human intestine, with distinct immunological niches.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-023-05915-x