Publications
Browse peer-reviewed literature, posters, webinars, blog articles, and more showing how we and others are using RepliGut Systems to support discovery.
2022
Burclaff, Joseph; Bliton, R. Jarrett; Breau, Keith A.; Ok, Meryem T.; Gomez-Martinez, Ismael; Ranek, Jolene S.; Bhatt, Aadra P.; Purvis, Jeremy E.; Woosley, John T.; Magness, Scott T.
A Proximal-to-Distal Survey of Healthy Adult Human Small Intestine and Colon Epithelium by Single-Cell Transcriptomics Journal Article
In: Cell Mol Gastroenterol Hepatol, vol. 13, no. 5, pp. 1554–1589, 2022, ISSN: 2352-345X.
Abstract | Links | BibTeX | Tags: Differentiate Cell Lineage, Enterochromaffin Cells, Enterocytes, Enteroendocrine Cells, Gut barrier function, Intestinal Epithelial Cells
@article{burclaff_proximal–distal_2022,
title = {A Proximal-to-Distal Survey of Healthy Adult Human Small Intestine and Colon Epithelium by Single-Cell Transcriptomics},
author = {Joseph Burclaff and R. Jarrett Bliton and Keith A. Breau and Meryem T. Ok and Ismael Gomez-Martinez and Jolene S. Ranek and Aadra P. Bhatt and Jeremy E. Purvis and John T. Woosley and Scott T. Magness},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043569/},
doi = {10.1016/j.jcmgh.2022.02.007},
issn = {2352-345X},
year = {2022},
date = {2022-02-15},
urldate = {2022-02-15},
journal = {Cell Mol Gastroenterol Hepatol},
volume = {13},
number = {5},
pages = {1554–1589},
abstract = {Background & 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 human beings.
Methods
A total of 12,590 single epithelial cells from 3 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 their capacity for response to extrinsic signals along the gut axis across different human beings.
Results
Cells were assigned to 25 epithelial lineage clusters. Multiple accepted intestinal stem cell markers do not specifically mark all human intestinal stem cells. Lysozyme expression is not unique to human Paneth cells, and Paneth cells lack expression of expected niche factors. Bestrophin 4 (BEST4)+ cells express Neuropeptide Y (NPY) and show maturational differences between the small intestine 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 junctions, and nutrient absorption genes show unappreciated regional expression differences across lineages. The differential expression of receptors and drug targets across lineages show biological variation and the 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 anatomic regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.},
keywords = {Differentiate Cell Lineage, Enterochromaffin Cells, Enterocytes, Enteroendocrine Cells, Gut barrier function, Intestinal Epithelial Cells},
pubstate = {published},
tppubtype = {article}
}
Background & 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 human beings.
Methods
A total of 12,590 single epithelial cells from 3 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 their capacity for response to extrinsic signals along the gut axis across different human beings.
Results
Cells were assigned to 25 epithelial lineage clusters. Multiple accepted intestinal stem cell markers do not specifically mark all human intestinal stem cells. Lysozyme expression is not unique to human Paneth cells, and Paneth cells lack expression of expected niche factors. Bestrophin 4 (BEST4)+ cells express Neuropeptide Y (NPY) and show maturational differences between the small intestine 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 junctions, and nutrient absorption genes show unappreciated regional expression differences across lineages. The differential expression of receptors and drug targets across lineages show biological variation and the 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 anatomic regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.
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 human beings.
Methods
A total of 12,590 single epithelial cells from 3 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 their capacity for response to extrinsic signals along the gut axis across different human beings.
Results
Cells were assigned to 25 epithelial lineage clusters. Multiple accepted intestinal stem cell markers do not specifically mark all human intestinal stem cells. Lysozyme expression is not unique to human Paneth cells, and Paneth cells lack expression of expected niche factors. Bestrophin 4 (BEST4)+ cells express Neuropeptide Y (NPY) and show maturational differences between the small intestine 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 junctions, and nutrient absorption genes show unappreciated regional expression differences across lineages. The differential expression of receptors and drug targets across lineages show biological variation and the 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 anatomic regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.
2014
Ahmad, Asad A.; Wang, Yuli; Gracz, Adam D.; Sims, Christopher E.; Magness, Scott T.; Allbritton, Nancy L.
Optimization of 3-D organotypic primary colonic cultures for organ-on-chip applications Journal Article
In: vol. 8, no. 1, pp. 9, 2014, ISSN: 1754-1611.
Abstract | Links | BibTeX | Tags: {PDMS}, {PDMS} Substrate, Colonic Crypt, Crypt Cell, Differentiate Cell Lineage
@article{ahmad_optimization_2014,
title = {Optimization of 3-D organotypic primary colonic cultures for organ-on-chip applications},
author = {Asad A. Ahmad and Yuli Wang and Adam D. Gracz and Christopher E. Sims and Scott T. Magness and Nancy L. Allbritton},
url = {https://doi.org/10.1186/1754-1611-8-9},
doi = {10.1186/1754-1611-8-9},
issn = {1754-1611},
year = {2014},
date = {2014-04-01},
urldate = {2023-02-20},
volume = {8},
number = {1},
pages = {9},
abstract = {New advances enable long-term organotypic culture of colonic epithelial stem cells that develop into structures known as colonoids. Colonoids represent a primary tissue source acting as a potential starting material for development of an in vitro model of the colon. Key features of colonic crypt isolation and subsequent colonoid culture have not been systematically optimized compromising efficiency and reproducibility. Here murine crypt isolation yield and quality are optimized, and colonoid culture efficiency measured in microfabricated culture devices.},
keywords = {{PDMS}, {PDMS} Substrate, Colonic Crypt, Crypt Cell, Differentiate Cell Lineage},
pubstate = {published},
tppubtype = {article}
}
New advances enable long-term organotypic culture of colonic epithelial stem cells that develop into structures known as colonoids. Colonoids represent a primary tissue source acting as a potential starting material for development of an in vitro model of the colon. Key features of colonic crypt isolation and subsequent colonoid culture have not been systematically optimized compromising efficiency and reproducibility. Here murine crypt isolation yield and quality are optimized, and colonoid culture efficiency measured in microfabricated culture devices.