Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in Human.
Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in Human.
复制标题
DOI：
10.1038/srep15118
复制
发表时间：
2015-10-12
影响因子：
4.6
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Chen Q;Ye W;Jian Tan W;Mei Yong KS;Liu M;Qi Tan S;Loh E;Te Chang K;Chye Tan T;Preiser PR;Chen J
对人类自然杀伤（NK）细胞发育的理解是不完整的，部分原因是获得适当的人体组织的机会有限。我们已经开发了一种精氨酸增强的人源化小鼠模型，其具有大大改善的人NK细胞的重建和功能。在这里，我们报告的细胞群的存在下，在骨髓中的马槟榔处理的人源化小鼠，表达NK细胞标志物CD 56和髓样标志物，如CD 36和CD 33。CD 56 + CD 33 + CD 36+细胞也存在于人脐带血、胎儿和成人骨髓中。虽然CD 56 + CD 33 + CD 36+细胞不表达常见的NK细胞功能性受体，并且表现出很少的细胞毒性和产生精氨酸的活性，但它们通过获得NK细胞受体的表达和失去髓样标志物的表达而容易分化为成熟的NK细胞。进一步的研究表明，CD 33 + CD 36+髓样NK前体细胞来源于粒-髓单核细胞祖细胞。这些结果描述了人NK细胞从骨髓中的髓系祖细胞分化的途径，并表明人源化小鼠用于研究人造血的效用。
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.