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Intestinal stem cells lacking the Math1 tumour suppressor are refractory to Notch inhibitors
- Source :
- Nature Communications, 1(2), 1-5. Nature Publishing Group, Nature Communications
- Publication Year :
- 2010
-
Abstract
- Intestinal cells are constantly produced from a stem cell reservoir that gives rise to proliferating transient amplifying cells, which subsequently differentiate into one of the four principal cell types. Signalling pathways, including the Notch signalling pathway, coordinate these differentiation processes and their deregulation may cause cancer. Pharmacological inhibition through γ-secretase inhibitors or genetic inactivation of the Notch signalling pathway results in the complete loss of proliferating crypt progenitors due to their conversion into post-mitotic goblet cells. The basic helix–loop–helix transcription factor Math1 is essential for intestinal secretory cell differentiation. Because of the critical roles of both Math1 and Notch signalling in intestinal homeostasis and neoplastic transformation, we sought to determine the genetic hierarchy regulating the differentiation of intestinal stem cells into secretory cells. In this paper, we demonstrate that the conversion of intestinal stem cells into goblet cells upon inhibition of the Notch signalling pathway requires Math1.<br />Notch inhibitors result in the differentiation of intestinal crypt progenitors into goblet cells, suggesting that they could be of use in treating intestinal neoplasia. Here van Es et al. show that Math1 is required for intestinal cell differentiation induced by Notch inhibition.
- Subjects :
- Cell type
Cellular differentiation
Notch signaling pathway
General Physics and Astronomy
Biology
In Vitro Techniques
General Biochemistry, Genetics and Molecular Biology
Article
Mice
Dibenzazepines
Basic Helix-Loop-Helix Transcription Factors
Animals
Neoplastic transformation
Progenitor cell
Transcription factor
In Situ Hybridization
Multidisciplinary
Receptors, Notch
Stem Cells
Cell Differentiation
General Chemistry
Immunohistochemistry
Cell biology
Intestines
biology.protein
Goblet Cells
Stem cell
Amyloid Precursor Protein Secretases
Amyloid precursor protein secretase
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 1
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....5dd0a18d3c64b94b4bbc6ef4beb3b7df