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. 2011 Mar 3;117(17):4449–4459. doi: 10.1182/blood-2010-06-290049

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© 2011 by The American Society of Hematology

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Dose-dependent Notch inhibition reveals a signal strength hierarchy. Effects of dose-dependent Notch inhibition on the induction of T-lineage differentiation (A), B-cell development (B), monocyte development (C), and plasmacytoid differentiation (pDC; D). Left panels: Flow cytometric analysis of human CD34⁺CD38⁻lin⁻ CB HPCs after OP9 coculture in the presence of 0 or 1μM GSI (7 N-[N-(3,5-difluorophenyl-L-alanyl]-S-phenylglycine t-butyl ester). Numbers in quadrants indicate the percentage of CD34⁺CD7⁺ T-cell precursors (A), CD19⁺HLA-DR⁺ B cells (B), CD14⁺CD4⁺ monocytes (C), and CD123⁺CD303⁺ pDCs (D). Results shown are representative of 3 independent experiments. Right panels: Corresponding average of the absolute number of CD34⁺CD7⁺ T-cell precursors (A), CD19⁺HLA-DR⁺ B cells (B), CD14⁺CD4⁺ monocytes (C), and CD123⁺CD303⁺ pDCs (D) for cultures depicted in the corresponding left panel. Error bars represent SEM. indicates an increasing dosage of GSI, corresponding to 0, 0.1, 0.3, and 1μM GSI.

Inline graphic — Dose-dependent Notch inhibition reveals a signal strength hierarchy. Effects of dose-dependent Notch inhibition on the induction of T-lineage differentiation (A), B-cell development (B), monocyte development (C), and plasmacytoid differentiation (pDC; D). Left panels: Flow cytometric analysis of human CD34⁺CD38⁻lin⁻ CB HPCs after OP9 coculture in the presence of 0 or 1μM GSI (7 N-[N-(3,5-difluorophenyl-L-alanyl]-S-phenylglycine t-butyl ester). Numbers in quadrants indicate the percentage of CD34⁺CD7⁺ T-cell precursors (A), CD19⁺HLA-DR⁺ B cells (B), CD14⁺CD4⁺ monocytes (C), and CD123⁺CD303⁺ pDCs (D). Results shown are representative of 3 independent experiments. Right panels: Corresponding average of the absolute number of CD34⁺CD7⁺ T-cell precursors (A), CD19⁺HLA-DR⁺ B cells (B), CD14⁺CD4⁺ monocytes (C), and CD123⁺CD303⁺ pDCs (D) for cultures depicted in the corresponding left panel. Error bars represent SEM. indicates an increasing dosage of GSI, corresponding to 0, 0.1, 0.3, and 1μM GSI.