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 ChenWeiruo 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, Michael Snyder

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish
Pages (from-to)572-584
Number of pages13
JournalNature
Volume619
Issue number7970
DOIs
StatePublished - Jul 20 2023

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