Organization of the human intestine at single-cell resolution

John W. Hickey, Winston R. Becker, Stephanie A. Nevins, Aaron Horning, Almudena Espin Perez, Chenchen Zhu, Bokai Zhu, Bei Wei, Roxanne Chiu, Derek C. Chen, Daniel L. Cotter, Edward D. Esplin, Annika K. Weimer, Chiara Caraccio, Vishal Venkataraaman, Christian M. Schürch, Sarah Black, Maria Brbić, Kaidi Cao, Shuxiao Chen, Weiruo Zhang, Emma Monte, Nancy R. Zhang, Zongming Ma, Jure Leskovec, Zhengyan Zhang, Shin Lin, Teri Longacre, Sylvia K. Plevritis, Yiing Lin, Garry P. Nolan (), William J. Greenleaf () and Michael Snyder ()
Additional contact information
John W. Hickey: Stanford School of Medicine
Winston R. Becker: Stanford School of Medicine
Stephanie A. Nevins: Stanford School of Medicine
Aaron Horning: Stanford School of Medicine
Almudena Espin Perez: Stanford School of Medicine
Chenchen Zhu: Stanford School of Medicine
Bokai Zhu: Stanford School of Medicine
Bei Wei: Stanford School of Medicine
Roxanne Chiu: Stanford School of Medicine
Derek C. Chen: Stanford School of Medicine
Daniel L. Cotter: Stanford School of Medicine
Edward D. Esplin: Stanford School of Medicine
Annika K. Weimer: Stanford School of Medicine
Chiara Caraccio: Stanford School of Medicine
Vishal Venkataraaman: Stanford School of Medicine
Christian M. Schürch: Stanford School of Medicine
Sarah Black: Stanford School of Medicine
Maria Brbić: Stanford University
Kaidi Cao: Stanford University
Shuxiao Chen: University of Pennsylvania
Weiruo Zhang: Stanford School of Medicine
Emma Monte: Stanford School of Medicine
Nancy R. Zhang: University of Pennsylvania
Zongming Ma: University of Pennsylvania
Jure Leskovec: Stanford University
Zhengyan Zhang: Washington University
Shin Lin: University of Washington
Teri Longacre: Stanford School of Medicine
Sylvia K. Plevritis: Stanford School of Medicine
Yiing Lin: Washington University
Garry P. Nolan: Stanford School of Medicine
William J. Greenleaf: Stanford School of Medicine
Michael Snyder: Stanford School of Medicine

Nature, 2023, vol. 619, issue 7970, 572-584

Abstract: Abstract The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health1. The intesting has a length of over nine metres, along which there are differences in structure and function2. 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.

Date: 2023
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DOI: 10.1038/s41586-023-05915-x

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