Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in Human

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Abstract

Understanding of natural killer (NK) cell development in human is incomplete partly because of limited access to appropriate human tissues. We have developed a cytokine-enhanced humanized mouse model with greatly improved reconstitution and function of human NK cells. Here we report the presence of a cell population in the bone marrow of the cytokine-treated humanized mice that express both NK cell marker CD56 and myeloid markers such as CD36 and CD33. The CD56+ CD33+ CD36+ cells are also found in human cord blood, fetal and adult bone marrow. Although the CD56+ CD33+ CD36+ cells do not express the common NK cell functional receptors and exhibit little cytotoxic and cytokine-producing activities, they readily differentiate into mature NK cells by acquiring expression of NK cell receptors and losing expression of the myeloid markers. Further studies show that CD33+ CD36+ myeloid NK precursors are derived from granulo-myelomonocytic progenitors. These results delineate the pathway of human NK cell differentiation from myeloid progenitors in the bone marrow and suggest the utility of humanized mice for studying human hematopoiesis.

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Chen, Q., Ye, W., Jian Tan, W., Mei Yong, K. S., Liu, M., Qi Tan, S., … Chen, J. (2015). Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in Human. Scientific Reports, 5. https://doi.org/10.1038/srep15118

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