Decoding the biological properties and transcriptomic landscapes of human natural killer cells derived from bone marrow and umbilical cord blood

解读源自骨髓和脐带血的人类自然杀伤细胞的生物学特性和转录组图

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作者:Baoguo Xie, Leisheng Zhang, Jianhua Gao, Ti'er Wang, Min Liu, Xiaoming Feng, Xianghong Xu, Shixun Ma, Hui Cai, Tiankang Guo, Weibin Huang, Xiaoyan Tu, Shuling Wang, Hongju Yang, Yihu Fang, Feifei Li, Cunrong Chen

Abstract

Longitudinal studies have highlighted allogeneic natural killer (NK) cell-based cytotherapy for cancer immunosurveillance and immunotherapy, yet the deficiency of systematic and detailed comparison of NK cells from candidate sources including umbilical cord blood (UC) and bone marrow (BM) largely hinders the large-scale application. Herein, we isolated resident NK cells (rUC-NK, rBM-NK) from mononuclear cells (MNC), and analyzed the corresponding expanded NK cell counterparts (eUC-NK, eBM-NK). Then, the eUC-NK and eBM-NK were turned to multifaceted bioinformatics from the aspects of gene expression profiling and genetic variations. The percentages of total or activated NK cells in rBM-NK group were approximate 2-fold higher over those in the rUC-NK group, respectively. Instead, the proportion of total NK cells in eUC-NK was higher than that in the eBM-NK group, and in particular, the CD25+ memory-like NK cell subset. Furthermore, eUC-NK and eBM-NK manifested multidimensional similarities and diversities in gene expression pattern and genetic spectrum, whereas both eUC-NK and eBM-NK exhibited effective tumor killing capacity. Collectively, we dissected the cellular and transcriptomic signatures of NK cells generated from UC-MNC and BM-MNC, which supplied new literature for further exploring the characteristics of the indicated NK cells and would benefit the clinical application for cancer immunotherapy in future.

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