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Single-cell profiling reveals the trajectories of natural killer cell differentiation in bone marrow and a stress signature induced by acute myeloid leukemia
Cellular & Molecular Immunology ( IF 21.8 ) Pub Date : 2020-11-25 , DOI: 10.1038/s41423-020-00574-8
Adeline Crinier 1 , Pierre-Yves Dumas 2, 3, 4 , Bertrand Escalière 1 , Christelle Piperoglou 5 , Laurine Gil 1 , Arnaud Villacreces 3, 4 , Frédéric Vély 1, 5 , Zoran Ivanovic 4, 6 , Pierre Milpied 1 , Émilie Narni-Mancinelli 1 , Éric Vivier 1, 5, 7
Affiliation  

Natural killer (NK) cells are innate cytotoxic lymphoid cells (ILCs) involved in the killing of infected and tumor cells. Among human and mouse NK cells from the spleen and blood, we previously identified by single-cell RNA sequencing (scRNAseq) two similar major subsets, NK1 and NK2. Using the same technology, we report here the identification, by single-cell RNA sequencing (scRNAseq), of three NK cell subpopulations in human bone marrow. Pseudotime analysis identified a subset of resident CD56bright NK cells, NK0 cells, as the precursor of both circulating CD56dim NK1-like NK cells and CD56bright NK2-like NK cells in human bone marrow and spleen under physiological conditions. Transcriptomic profiles of bone marrow NK cells from patients with acute myeloid leukemia (AML) exhibited stress-induced repression of NK cell effector functions, highlighting the profound impact of this disease on NK cell heterogeneity. Bone marrow NK cells from AML patients exhibited reduced levels of CD160, but the CD160high group had a significantly higher survival rate.



中文翻译:

单细胞分析揭示了骨髓中自然杀伤细胞分化的轨迹和急性髓性白血病诱导的应激特征

自然杀伤 (NK) 细胞是参与杀死受感染细胞和肿瘤细胞的先天性细胞毒性淋巴细胞 (ILC)。在来自脾脏和血液的人和小鼠 NK 细胞中,我们之前通过单细胞 RNA 测序 (scRNAseq) 鉴定了两个相似的主要亚群 NK1 和 NK2。使用相同的技术,我们在此报告通过单细胞 RNA 测序 (scRNAseq) 鉴定人骨髓中的三个 NK 细胞亚群。伪时间分析确定了一部分常驻 CD56NK 细胞,NK0 细胞,作为循环 CD56NK1 样 NK 细胞和 CD56亮的前体生理条件下人骨髓和脾脏中的NK2样NK细胞。来自急性髓性白血病 (AML) 患者的骨髓 NK 细胞的转录组图表现出应激诱导的 NK 细胞效应功能抑制,突出了这种疾病对 NK 细胞异质性的深远影响。来自 AML 患者的骨髓 NK 细胞表现出 CD160 水平降低,但 CD160组具有显着更高的存活率。

更新日期:2020-11-25
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