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Intestinal stem cells lacking the Math1 tumour suppressor are refractory to Notch inhibitors

Es van, J.H. and Geest de, N. and Born van den, M.M.W. and Clevers, H. and Hassan, B. A. (2010) Intestinal stem cells lacking the Math1 tumour suppressor are refractory to Notch inhibitors. Nature Communications, 1, 1-5. ISSN 2041-1723.

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Official URL: http://dx.doi.org/10.1038/ncomms1017

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 gamma-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.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:9477
Deposited On:04 Jan 2011 01:00
Last Modified:07 Sep 2011 17:01

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