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| Status |
Public on Feb 21, 2022 |
| Title |
A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
Results: 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.
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| Overall design |
Single cell RNA sequencing libraries from epithelium isolated from Duodenum, Jejunum, Ileum, Ascending Colon, Transverse Colon, and Descending Colon from each of 3 human organ donors were compiled
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| Contributor(s) |
Burclaff J, Bliton RJ, Breau KA, Ok MT, Gomez-Martinez I, Ranek JS, Bhatt AP, Purvis JE, Woosley JT, Magness ST |
| Citation(s) |
35176508 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 DK115806 |
Genetic regulation of active and reserve intestinal stem cell states |
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL |
SCOTT T MAGNESS |
| R01 DK109559 |
DEVELOPMENT OF HUMAN INTESTINAL SIMULACRA |
UNIVERSITY OF WASHINGTON |
SCOTT T MAGNESS |
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| Submission date |
Oct 03, 2021 |
| Last update date |
Dec 09, 2022 |
| Contact name |
Jarrett Bliton |
| E-mail(s) |
jarrett@altisbiosystems.com
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| Organization name |
Altis Biosystems
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| Street address |
6 Davis Drive
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| City |
Durham |
| ZIP/Postal code |
27709 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA768275 |
| SRA |
SRP339818 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE185224_Donor1_filtered_feature_bc_matrix.h5 |
25.7 Mb |
(ftp)(http) |
H5 |
| GSE185224_Donor2_filtered_feature_bc_matrix.h5 |
30.6 Mb |
(ftp)(http) |
H5 |
| GSE185224_Donor3_filtered_feature_bc_matrix.h5 |
23.5 Mb |
(ftp)(http) |
H5 |
| GSE185224_Donors_IntestinalRegions_Hashtags.txt.gz |
383 b |
(ftp)(http) |
TXT |
| GSE185224_clustered_annotated_adata_k10_lr0.92_v1.7.h5ad.gz |
1.3 Gb |
(ftp)(http) |
H5AD |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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