Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in Human

• Main Authors: Chen, Qingfeng, Ye, Weijian, Liu, Min, Tan, Shu Qi, Loh, Eva, Chang, Kenneth T. E., Tan, Thiam Chye, Preiser, Peter R., Tan, Wei Jian, Yong, Kylie Su Mei, Chen, Jianzhu
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2015
• Online Access: https://hdl.handle.net/10356/81095; http://hdl.handle.net/10220/39052
• Institution: Nanyang Technological University

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.