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GEO help: Mouse over screen elements for information. |
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Status |
Public on Aug 15, 2013 |
Title |
Non-neuronal acetylcholine as an endogenous regulator of proliferation and differentiation of Lgr5-positive stem cells in mice |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Acetylcholine (ACh) has been considered a neurotransmitter residing in central, parasympathetic and neuromuscular synapses of mammals. Here, experiments using crypt-villus organoids that lack nerve and immune cells in culture led us to suggest that endogenous ACh is synthesized in the intestinal epithelium to evoke growth and differentiation of the organoids through activation of muscarinic ACh receptors (mAChRs). The extracts of the cultured organoids exhibit a noticeable capacity for ACh synthesis that is sensitive to a potent inhibitor of choline acetyltransferase (ChAT). Imaging mass spectrometry reveals distribution of endogenous ACh that is localized in intestinal epithelial layer in the cultured organoids as well as in mouse small intestinal epithelium in vivo, suggesting non-neural resources of ACh. Treatment of organoids with carbachol down-regulates growth of organoids and expression of marker gene for each epithelial cell. On the other hand, antagonists for mAChRs enhances growth and differentiation of organoids, indicating involvement of mAChRs in regulating proliferation and differentiation of Lgr5-positive stem cells. Collectively, our data provide evidence that endogenous ACh released from intestinal epithelium maintains homeostasis of intestinal epithelial cell growth and differentiation via mAChRs in mice.
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Overall design |
Gene expression patters of gut, crypt, y-organoid and o-organoid, respectively
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Contributor(s) |
Takahashi T, Ohnishi H, Sugiura Y, Honda K, Suematsu M, Kawakami T, Deguchi T, Fujii T, Yamagaki T, Yuba S |
Citation(s) |
25143155 |
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Submission date |
Aug 14, 2013 |
Last update date |
Jan 19, 2018 |
Contact name |
Toshio Takahashi |
E-mail(s) |
takahashi@sunbor.or.jp
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Organization name |
Suntory Foundation for Life Sciences
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Street address |
1-1-1 Wakayamadai
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City |
Osaka |
ZIP/Postal code |
618-8503 |
Country |
Japan |
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Platforms (1) |
GPL10333 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Feature Number version) |
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Samples (4)
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Relations |
BioProject |
PRJNA215161 |
Supplementary file |
Size |
Download |
File type/resource |
GSE49864_RAW.tar |
42.2 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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