Journal
STEM CELLS
Volume 25, Issue 10, Pages 2488-2497Publisher
WILEY
DOI: 10.1634/stemcells.2007-0102
Keywords
umbilical cord blood; Wnt; Notch; natural killer cells; T cells
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Funding
- NHLBI NIH HHS [P50HL54881, K23 HL0774446, P01 HL084205, R01 HL080245] Funding Source: Medline
- NICHD NIH HHS [1 F32 HD049208-01] Funding Source: Medline
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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 more cells with T or natural killer ( 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 epsilon and preT alpha. In contrast, culture with Wnt3a alone did not increase generation of CD34(-) CD7(+) precursors or expression of CD3 epsilon or preT alpha 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 that regulation of Notch signaling by the Wnt pathway plays a critical role in differentiation of precursors along the early T or NK differentiation pathways.
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