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EMBRYONIC STEM CELLS

Notch Signaling Is Inactive but Inducible in Human Embryonic Stem Cells

^cInstitute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia, USA;
^bBresaGen Inc., Athens, Georgia, USA;
^aDepartment of Genetics, University of Georgia, Athens, Georgia, USA

Key Words. Differentiation • -Secretase • Human embryonic stem cell • Human development • NOTCH intracellular domain • HES

Correspondence: Brian G. Condie, Ph.D.,Department of Genetics, University of Georgia, Davison Life Sciences Complex, Athens, Georgia 30602, USA. Telephone: 706-542-1431; Fax: 706-583-0691; email: bcondie{at}uga.edu

Received on July 12, 2005; accepted for publication on March 21, 2006.

First published online in STEM CELLS EXPRESS  April 13, 2006.

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 (hESCs) has not been tested. We measured the activity of canonical NOTCH signaling in undifferentiated embryonic stem (ES) cells and tested the requirement for NOTCH activity in hESC self-renewal or differentiation by growing hESCs in the presence of -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.

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