RT Journal Article
SR Electronic
T1 A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.05.460818
DO 10.1101/2021.10.05.460818
A1 Joseph Burclaff
A1 R. Jarrett Bliton
A1 Keith A Breau
A1 Meryem T Ok
A1 Ismael Gomez-Martinez
A1 Jolene S Ranek
A1 Aadra P Bhatt
A1 Jeremy E Purvis
A1 John T Woosley
A1 Scott T Magness
YR 2021
UL http://biorxiv.org/content/early/2021/10/06/2021.10.05.460818.abstract
AB Background and 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 humans.Methods 12,590 single epithelial cells from three 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 capacity for response to extrinsic signals along the gut axis across different humans.Result Cells were assigned to 25 epithelial lineage clusters. Human intestinal stem cells (ISCs) are not specifically marked by many murine ISC markers. Lysozyme expression is not unique to human Paneth cells (PCs), and PCs lack expression of expected niche-factors. BEST4+ cells express NPY and show maturational differences between SI 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-junction, and nutrient absorption genes show unappreciated regional expression differences across lineages. Differential expression of receptors and drug targets across lineages reveals biological variation and 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 anatomical regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.Competing Interest StatementThe authors have declared no competing interest.SISmall intestinescRNAseqsingle-cell RNA sequencingACAscending ColonTCTransverse ColonDCDescending ColonPCPaneth CellFAEFollicle Associated EpitheliumEECEnteroendocrine CellGCGoblet CellDEGDifferentially Expressed GenesISCIntestinal Stem CellTATransit AmplifyingACCAbsorptive ColonocyteAEAbsorptive EnterocytePAGAPartition-based Graph AbstractionM-cellMicrofold CellGIGastrointestinalcrGCCrypt-Resident Goblet CellicGCInter-Crypt Goblet Cell