Porcine colonoids and enteroids keep the memory of their origin during regeneration

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Date
2021-05-01
Open Access Location
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Publisher
American Physiological Society
Rights
(c) 2021 The Author/s
CC BY 4.0
Abstract
The development of alternative in vitro culture methods has increased in the last decade as three-dimensional organoids of various tissues, including those of the small and large intestines. Due to their multicellular composition, organoids offer advantages over traditionally used immortalized or primary cell lines. However, organoids must be accurate models of their tissues of origin. This study compared gene expression profiles with respect to markers of specific cell types (stem cells, enterocytes, goblet, and enteroendocrine cells) and barrier maturation (tight junctions) of colonoid and enteroid cultures with their tissues of origin and colonoids with enteroids. Colonoids derived from three healthy pigs formed multilobed structures with a monolayer of cells similar to the crypt structures in colonic tissue. Colonoid and enteroid gene expression signatures were more similar to those found for the tissues of their origin than to each other. However, relative to their derived tissues, organoids had increased gene expression levels of stem cell markers Sox9 and Lgr5 encoding sex-determining region Y-box 9 and leucine-rich repeat-containing G protein-coupled rector 5, respectively. In contrast, expression levels of Occl and Zo1 encoding occludin and zonula occludens 1, respectively, were decreased. Expression levels of the cell lineage markers Atoh1, Cga, and Muc2 encoding atonal homolog 1, chromogranin A, and mucin 2, respectively, were decreased in colonoids, whereas Sglt1 and Apn encoding sodium-glucose transporter 1 and aminopeptidase A, respectively, were decreased in enteroids. These results indicate colonoid and enteroid cultures were predominantly comprised of undifferentiated cell types with decreased barrier maturation relative to their tissues of origin.
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Keywords
barrier maturation, colon, differentiation, intestinal epithelium, stem cells, Animals, Biomarkers, Cell Differentiation, Cell Lineage, Cell Proliferation, Colon, Gene Expression Regulation, Ileum, Intestinal Mucosa, Male, Organoids, Phenotype, Signal Transduction, Sus scrofa, Time Factors, Tissue Culture Techniques, Transcriptome
Citation
Barnett AM, Mullaney JA, Hendriks C, Le Borgne L, McNabb WC, Roy NC. (2021). Porcine colonoids and enteroids keep the memory of their origin during regeneration.. Am J Physiol Cell Physiol. 320. 5. (pp. C794-C805).
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