Zhang Leisheng, Yang Sijun, Chen Hongjun, Xue Chun'e, Wang Ti'er, Chen Shuang, Xu Xianghong, Ma Shixun, Yu Miao, Guo Tiankang, Han Yan, Yan Jianhui, Shen Jiakun, Cai Hui, Li Feifei
School of Medicine, Nankai University Tianjin 300071, China.
Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province & National Health Commission (NHC) Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital Lanzhou 730000, Gansu, China.
Am J Cancer Res. 2023 Aug 15;13(8):3531-3546. eCollection 2023.
Longitudinal studies have indicated the pivotal role of natural killer cells (NKs) in the elimination of certain infections and malignancies. Currently, perinatal blood (PB) and cord blood (CB) have been considered with promising prospective for autogenous and allogeneic NKs transplantation, yet the similarities and differences at the biological and molecular levels are largely obscure. We isolated mononuclear cells (MNCs) from PB and CB, and compared the biological phenotypes of resident NKs by flow cytometry and cell counting. Then, we turned to our well-established "3ILs" strategy and co-culture for NK cell activation and cytotoxicity analyses, respectively. Finally, with the aid of transcriptomic analyses, we further dissected the signatures of PB-NKs and CB-NKs. CB-NKs revealed superiority in cellular vitality over PB-NKs, together with variations in subpopulations. CB-NKs showed higher cytotoxicity over PB-NKs against K562 cells. Furthermore, we found both NKs revealed multifaceted conservations and differences in gene expression profiling and genetic variations, together with gene subsets and signaling pathway. Collectively, both NKs revealed multifaceted similarities and diverse variations at the cellular and transcriptomic levels. Our findings would benefit the further exploration of the biological and transcriptomic properties of CB-NKs and PB-NKs, together with the development of NK cell-based cytotherapy.
纵向研究表明自然杀伤细胞(NK细胞)在清除某些感染和恶性肿瘤中起关键作用。目前,围产期血液(PB)和脐带血(CB)被认为在自体和异体NK细胞移植方面具有广阔前景,但它们在生物学和分子水平上的异同很大程度上仍不清楚。我们从PB和CB中分离出单核细胞(MNC),并通过流式细胞术和细胞计数比较了驻留NK细胞的生物学表型。然后,我们采用成熟的“3ILs”策略并分别进行共培养以分析NK细胞的活化和细胞毒性。最后,借助转录组分析,我们进一步剖析了PB-NK细胞和CB-NK细胞的特征。CB-NK细胞在细胞活力方面优于PB-NK细胞,且亚群存在差异变动。在针对K562细胞方面,CB-NK细胞比PB-NK细胞表现出更高的细胞毒性。此外,我们发现两种NK细胞在基因表达谱、遗传变异以及基因子集和信号通路方面都存在多方面的保守性和差异。总体而言,两种NK细胞在细胞和转录组水平上都表现出多方面的相似性和多样的差异。我们的研究结果将有助于进一步探索CB-NK细胞和PB-NK细胞的生物学和转录组特性,以及基于NK细胞的细胞疗法的发展。