1. Delta-like 1 expression promotes goblet cell differentiation in Notch-inactivated human colonic epithelial cells
- Author
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Shiro Yui, Xiu Zheng, Mamoru Watanabe, Michiko Iwasaki, Kiichiro Tsuchiya, Junko Akiyama, Tetsuya Nakamura, and Ryuichi Okamoto
- Subjects
ATOH1 ,Colon ,Cellular differentiation ,Biophysics ,Notch signaling pathway ,Cell fate determination ,Biochemistry ,Basic Helix-Loop-Helix Transcription Factors ,medicine ,Humans ,Molecular Biology ,Cells, Cultured ,Homeodomain Proteins ,Goblet cell ,Gene knockdown ,Receptors, Notch ,biology ,Chemistry ,Calcium-Binding Proteins ,Membrane Proteins ,Cell Differentiation ,Cell Biology ,Phenotype ,Up-Regulation ,Cell biology ,medicine.anatomical_structure ,Gene Knockdown Techniques ,biology.protein ,Intercellular Signaling Peptides and Proteins ,Transcription Factor HES-1 ,Goblet Cells ,Signal transduction ,Signal Transduction - Abstract
Notch signaling has previously been implicated in the regulation of the cell fate of intestinal epithelial cells. However, the expression and function of Notch ligands in the human intestine remain largely unknown. In the present study, we showed that Notch ligands Delta-like 1 (Dll1) and Delta-like 4 (Dll4) are expressed in a goblet cell-specific manner in human colonic tissue. Additionally, we found that Dll1 and Dll4 expression was regulated in-parallel with Atoh1 and MUC2, which are both under the control of the Notch-Hes1 signaling pathway. Because knockdown of Dll1 expression completely abrogated the acquisition of the goblet cell phenotype in Notch-inactivated colonic epithelial cells, we postulate that Dll1 might function as a cis-acting regulatory element that induces undifferentiated cells to become goblet cells. Our results suggest a link between Dll1 expression and human goblet cell differentiation that might be mediated by a function that is distinct from its role as a Notch receptor ligand.
- Published
- 2010