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First published online April 13, 2006
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2005-0314v1
24/7/1646    most recent
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Submitted on July 12, 2005
Accepted on March 21, 2006

Embryonic Stem Cells

NOTCH signaling is inactive but inducible in human embryonic stem cells

Scott A. Noggle 1, Deborah Weiler 2, Brian G. Condie 3*

1 Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia
2 BresaGen, Inc., Athens, Georgia
3 Department of Genetics, University of Georgia, Athens, Georgia

* To whom correspondence should be addressed. E-mail: bcondie{at}uga.edu.


   Abstract

The NOTCH signaling pathway performs a wide range of critical functions in a number of different cell types during development and differentiation. The role of NOTCH signals in human embryonic stem cells (hESC) has not been tested. We measured the activity of canonical NOTCH signaling in undifferentiated ES cells and tested the requirement for NOTCH activity in hESC self renewal or differentiation by growing hESC in the presence of {gamma}-secretase inhibitors. Our results suggest that NOTCH signaling is not required for the propagation of undifferentiated human ES cells but instead is required for the maintenance of the differentiating cell types that accumulate in human ES cell cultures. Our studies suggest that NOTCH signaling is not required in human embryonic differentiation until the formation of extraembryonic, germ layer or tissue specific stem cells and progenitors.

Key Words. differentiation, {gamma}-secretase, hESC, human development, NICD, Hes




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