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|Title:||A novel role for γ-secretase in the formation of primitive streak-like intermediates from ES cells in culture|
|Other Titles:||A novel role for gamma-secretase in the formation of primitive streak-like intermediates from ES cells in culture|
|Citation:||Stem Cells, 2009; 27(12):2941-2951|
|James N. Hughes, Natasha Dodge, Peter D. Rathjen and Joy Rathjen|
|Abstract:||Υ-Secretase is a membrane-associated protease with multiple intracellular targets, a number of which have been shown to influence embryonic development and embryonic stem (ES) cell differentiation. This paper describes the use of the Υ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) to evaluate the role of Υ- secretase in the differentiation of pluripotent stem cells to the germ lineages. The addition of DAPT did not prevent the formation of primitive ectoderm-like cells from ES cells in culture. In contrast, the addition of DAPT during primitive ectoderm-like cell differentiation interfered with the ability of both serum and BMP4 to induce a primitive streak-like intermediate and resulted in the preferential formation of neurectoderm. Similarly, DAPT reduced the formation of primitive streak-like intermediates from differentiating human ES cells; the culture conditions used resulted in a population enriched in human surface ectoderm. These data suggest that Υ-secretase may form part of the general pathway by which mesoderm is specified within the primitive streak. The addition of an E-cadherin neutralizing antibody was able to partially reverse the effect of DAPT, suggesting that DAPT may be preventing the formation of primitive streak-like intermediates and promoting neurectoderm differentiation by stabilizing E-cadherin and preventing its proteolysis.|
|Keywords:||Embryonic stem cell|
|Rights:||Copyright © 2009 AlphaMed Press|
|Appears in Collections:||Aurora harvest|
Molecular and Biomedical Science publications
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