Journal
OPEN BIOLOGY
Volume 8, Issue 4, Pages -Publisher
ROYAL SOC
DOI: 10.1098/rsob.170256
Keywords
intestinal epithelium; differentiation; AMPK; LGR5; stem cell; migration
Categories
Funding
- National Institutes of Health (NIH) [R15HD073864]
- USDA National Institute of Food and Agriculture (USDA-NIFA) [2018-67017-27517]
- Emerging Research Issues Internal Competitive grant from the Washington State University, Agricultural Research Center [10A-3057-8640]
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Epithelial cultures are commonly used for studying gut health. However, due to the absence of mesenchymal cells and gut structure, epithelial culture systems including recently developed three-dimensional organoid culture cannot accurately represent in vivo gut development, which requires intense cross-regulation of the epithelial layer with the underlying mesenchymal tissue. In addition, organoid culture is costly. To overcome this, a new culture system was developed using mouse embryonic small intestine. Cultured intestine showed spontaneous peristalsis, indicating the maintenance of the normal gut physiological structure. During 10 days of ex vivo culture, epithelial cells moved along the gut surface and differentiated into different epithelial cell types, including enterocytes, Paneth cells, goblet cells and enteroendocrine cells. We further used the established ex vivo system to examine the role of AMP-activated protein kinase (AMPK) on gut epithelial health. Tamoxifen-induced AMPK alpha 1 knockout vastly impaired epithelial migration and differentiation of the developing ex vivo gut, showing the crucial regulatory function of AMPK alpha 1 in intestinal health.
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