Single-cell profiling reveals the trajectories of natural killer cell differentiation in bone marrow and a stress signature induced by acute myeloid leukemia.

Single-cell profiling reveals the trajectories of natural killer cell differentiation in bone marrow and a stress signature induced by acute myeloid leukemia.
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DOI:
10.1038/s41423-020-00574-8
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发表时间:
2021-05
影响因子:
24.1
通讯作者:
Vivier É
Vivier É
中科院分区:
医学1区
文献类型:
--
作者:
Crinier A;Dumas PY;Escalière B;Piperoglou C;Gil L;Villacreces A;Vély F;Ivanovic Z;Milpied P;Narni-Mancinelli É;Vivier É

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自然杀伤(NK)细胞是天然的细胞毒性淋巴样细胞(ILCs),参与对感染细胞和肿瘤细胞的杀伤。在人和小鼠脾和血中的NK细胞中,我们先前通过单细胞RNA测序(ScRNAseq)鉴定了两个相似的主要亚群NK1和NK2。然后使用相同的技术,我们报告了通过单细胞RNA测序(ScRNAseq)鉴定人骨髓中的三个NK细胞亚群。假时间分析证实,在生理条件下,人骨髓和脾中的CD56bright NK细胞亚群NK0细胞是循环中CD56dim NK1样NK细胞和CD56bright NK2样NK细胞的前体细胞。急性髓系白血病(AML)患者骨髓NK细胞的转录谱显示应激诱导的NK细胞效应功能抑制,突出了这种疾病对NK细胞异质性的深刻影响。AML患者骨髓NK细胞CD160表达水平降低,但CD160高表达组存活率显著高于对照组。
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.
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