The present invention in general relates to a method of differentiating human hematopoietic stem cells (HSC) into mature natural killer (NK) cells; wherein said method is in particular characterized in that mature NK cells are obtainable very early during the differentiation method, and that these NK cells display increased CD16 expression and antibody-dependent cellular cytotoxicity (ADCC) (figure 11). The method of the invention specifically encompasses transfecting and/or transducing HSCs with at least one transcription factor selected from T- Box expressed in T cells (T-BET) and Eomesodermin (EOMES); or a combination thereof.
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