Panoramic comparison between NK cells in healthy and cancerous liver through single-cell RNA sequencing.
Panoramic comparison between NK cells in healthy and cancerous liver through single-cell RNA sequencing.
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通过单细胞RNA测序全景比较健康和癌症肝脏中的NK细胞。
DOI：
10.20892/j.issn.2095-3941.2022.0050
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发表时间：
2022-07-21
影响因子：
5.5
通讯作者：
Sun, Rui
中科院分区：
文献类型：
--
作者：
Liu, Huan;Zhao, Ronghua;Qin, Rongrong;Sun, Haoyu;Huang, Qiang;Liu, Lianxin;Tian, Zhigang;Nashan, Bjorn;Sun, Cheng;Sun, Rui
NK细胞在针对病毒感染和转化细胞的免疫防御机制中起着至关重要的作用。然而，肝脏NK细胞的发育进程、转录组学景观和功能亚型还没有很好的定义。肝细胞癌（HCC）约占全球原发性肝癌的80%，但HCC环境中NK细胞的生物学特性尚不清楚。因此，我们的目的是确定这些细胞在肿瘤发生和预后中的作用。我们比较了从血液（n = 1）、健康肝组织（n = 3）、HCC肿瘤组织（n = 4）和瘤周肝组织（n = 1）纯化的NK细胞的单细胞RNA测序谱，以鉴定NK细胞亚群。此外，我们通过使用癌症基因组图谱（TCGA）数据进行生物信息学分析，以确定HCC患者血液和肿瘤组织中同时过表达的预后生物标志物。转录组学分析显示健康肝组织中存在5个NK细胞亚群（L1-NK-CD 56 bright、L2-NK-CD 56 dim、L3-NK-HLA、L4-LrNK-FCGR 3A和L5-LrNK-XCL 1）。而在肝癌组织和癌旁肝组织中，未见具有较强抗肿瘤活性的移行L3亚群和CXCR 6 + CD 16 + L4亚群。此外，4种常见的肿瘤相关基因（RHOB、TALDO 1、HLA-DPA 1和TKT）在配对的肿瘤组织和血液中显著过表达。我们的研究揭示了健康人肝组织中5种特异性NK细胞亚群。然而，5个NK细胞亚群中只有3个存在于HCC和癌旁组织中。细胞毒NK细胞亚群在HCC组织中缺失。此外，我们确定了4个潜在的非侵入性预后生物标志物在肝癌患者。
NK cells play crucial roles in the immune defense mechanisms against viral infections and transformed cells. However, the developmental progression, transcriptomic landscape, and functional subtypes of liver NK cells are not well defined. Hepatocellular carcinoma (HCC) accounts for approximately 80% of primary liver cancer worldwide, yet the biological characteristics of NK cells in the HCC environment are unclear. Therefore, we aimed to determine these cells’ roles in tumorigenesis and prognosis. We compared the single-cell RNA sequencing profiles of NK cells purified from blood (n = 1), healthy liver tissues (n = 3), HCC tumor tissues (n = 4), and peritumor liver tissues (n = 1) to identify NK cell subsets. Furthermore, we performed bioinformatics analysis by using The Cancer Genome Atlas (TCGA) data to identify prognostic biomarkers simultaneously overexpressed in the blood and tumor tissues of patients with HCC. Transcriptomic analysis revealed 5 NK cell subsets (L1-NK-CD56bright, L2-NK-CD56dim, L3-NK-HLA, L4-LrNK-FCGR3A, and L5-LrNK-XCL1) in the healthy liver tissues. However, the transitional L3 subset and the CXCR6+CD16+ L4 subset with strong anti-tumor activity were absent in the HCC and peritumor liver tissues. Furthermore, 4 common prognosis-associated genes (RHOB, TALDO1, HLA-DPA1, and TKT) were significantly overexpressed in the paired tumor tissue and blood. Our study revealed 5 specific subsets of NK cells in healthy human liver tissues. However, only 3 of the 5 NK cell subsets were present in HCC and peritumor tissues. The cytotoxic NK cell subsets were absent in HCC tissues. Furthermore, we identified 4 potential non-invasive prognostic biomarkers in patients with HCC.
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影响因子：
16.6
作者：
MacParland SA;Liu JC;Ma XZ;Innes BT;Bartczak AM;Gage BK;Manuel J;Khuu N;Echeverri J;Linares I;Gupta R;Cheng ML;Liu LY;Camat D;Chung SW;Seliga RK;Shao Z;Lee E;Ogawa S;Ogawa M;Wilson MD;Fish JE;Selzner M;Ghanekar A;Grant D;Greig P;Sapisochin G;Selzner N;Winegarden N;Adeyi O;Keller G;Bader GD;McGilvray ID
通讯作者：
McGilvray ID
影响因子：
4
作者：
Erokhina SA;Streltsova MA;Kanevskiy LM;Telford WG;Sapozhnikov AM;Kovalenko EI
通讯作者：
Kovalenko EI
影响因子：
6.7
作者：
Han, Jing;Chen, Congcong;Hu, Zhibin
通讯作者：
Hu, Zhibin
影响因子：
12.8
作者：
Hudspeth K;Donadon M;Cimino M;Pontarini E;Tentorio P;Preti M;Hong M;Bertoletti A;Bicciato S;Invernizzi P;Lugli E;Torzilli G;Gershwin ME;Mavilio D
通讯作者：
Mavilio D
高维单细胞分析确定了人和小鼠中器官特异性的特异性特异性特异性特异性特异性特异性特异性特异性标志和保守的NK细胞子集。
影响因子：
32.4
作者：
Crinier A;Milpied P;Escalière B;Piperoglou C;Galluso J;Balsamo A;Spinelli L;Cervera-Marzal I;Ebbo M;Girard-Madoux M;Jaeger S;Bollon E;Hamed S;Hardwigsen J;Ugolini S;Vély F;Narni-Mancinelli E;Vivier E
通讯作者：
Vivier E