The Interaction of The Wnt and Notch Pathways Modulates Nk vs. T Cell Differentiation

¹ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
² Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195
³ Howard Hughes Medical Institute, Department of Pharmacology, and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98195, Division of Hematology, University of Washington School of Medicine, Seattle, WA 98195
⁴ Howard Hughes Medical Institute, Department of Pharmacology, and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98195

^* To whom correspondence should be addressed. E-mail: ibernste{at}fhcrc.org.

	Abstract

The Wnt and Notch signaling pathways have been independently shown to play a critical role in regulating hematopoietic cell fate decisions. We previously reported that induction of Notch signaling in human CD34⁺CD38^- cord blood cells by culture with the Notch ligand Delta1 resulted in an increased number of cells with T or NK lymphoid precursor phenotype. Here we show that addition of Wnt3a to Delta1 further increased the percentage of CD34^-CD7⁺ and CD34^-CD7⁺cyCD3⁺ cells with increased expression of CD3 and preT. In contrast, culture with Wnt3a alone did not increase generation of CD34^-CD7⁺ precursors or expression of CD3 or preT gene. Furthermore, Wnt3a increased the amount of activated Notch1, suggesting that Wnt modulates Notch signaling by affecting Notch protein levels. In contrast, addition of a Wnt signaling inhibitor to Delta1 increased the percentage of CD56⁺ NK cells. Overall these results demonstrate regulation of Notch signaling by the Wnt pathway plays a critical role in differentiation of precursors along the early T or NK differentiation pathway.

This article has been cited by other articles:

				C. S. Jayasena, T. Ohyama, N. Segil, and A. K. Groves Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode Development, July 1, 2008; 135(13): 2251 - 2261. [Abstract] [Full Text] [PDF]