Single-Cell, Single-Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity.
Single-Cell, Single-Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity.
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DOI：
10.1002/hep4.1854
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发表时间：
2022-04
影响因子：
5.1
通讯作者：
MacParland SA
中科院分区：
文献类型：
--
作者：
Andrews TS;Atif J;Liu JC;Perciani CT;Ma XZ;Thoeni C;Slyper M;Eraslan G;Segerstolpe A;Manuel J;Chung S;Winter E;Cirlan I;Khuu N;Fischer S;Rozenblatt-Rosen O;Regev A;McGilvray ID;Bader GD;MacParland SA
人类肝脏的关键功能通过肝实质细胞和非实质细胞的相互作用来协调。单细胞转录方法的最新进展使人类肝脏的检查具有前所未有的分辨率。然而，解离相关的细胞扰动可能限制完全捕获人肝脏实质细胞部分的能力，这限制了全面分析该器官的能力。在这里，我们使用匹配的单细胞RNA测序（scRNA-seq）和单核RNA测序（snRNA-seq）报告了来自人类肝脏的73，295个细胞的转录景观。snRNA-seq的添加使得能够以单细胞分辨率表征带间肝细胞，揭示了肝脏间充质细胞的罕见亚型的存在，并促进了仅在体外分化实验期间观察到的胆管祖细胞的检测。然而，T和B淋巴细胞和自然杀伤细胞只能使用scRNA-seq区分，这突出了应用这两种技术以获得组织驻留细胞类型的完整图谱的重要性。我们通过独立的空间转录组学数据集和免疫组织化学验证了肝细胞、胆管细胞和间充质细胞群体的不同空间分布。结论：我们的研究提供了scRNA-seq和snRNA-seq捕获的转录组的系统比较，并提供了健康人类肝脏中实质细胞群的高分辨率图谱。
The critical functions of the human liver are coordinated through the interactions of hepatic parenchymal and non‐parenchymal cells. Recent advances in single‐cell transcriptional approaches have enabled an examination of the human liver with unprecedented resolution. However, dissociation‐related cell perturbation can limit the ability to fully capture the human liver’s parenchymal cell fraction, which limits the ability to comprehensively profile this organ. Here, we report the transcriptional landscape of 73,295 cells from the human liver using matched single‐cell RNA sequencing (scRNA‐seq) and single‐nucleus RNA sequencing (snRNA‐seq). The addition of snRNA‐seq enabled the characterization of interzonal hepatocytes at a single‐cell resolution, revealed the presence of rare subtypes of liver mesenchymal cells, and facilitated the detection of cholangiocyte progenitors that had only been observed during in vitro differentiation experiments. However, T and B lymphocytes and natural killer cells were only distinguishable using scRNA‐seq, highlighting the importance of applying both technologies to obtain a complete map of tissue‐resident cell types. We validated the distinct spatial distribution of the hepatocyte, cholangiocyte, and mesenchymal cell populations by an independent spatial transcriptomics data set and immunohistochemistry. Conclusion: Our study provides a systematic comparison of the transcriptomes captured by scRNA‐seq and snRNA‐seq and delivers a high‐resolution map of the parenchymal cell populations in the healthy human liver.
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影响因子：
64.8
作者：
Halpern KB;Shenhav R;Matcovitch-Natan O;Toth B;Lemze D;Golan M;Massasa EE;Baydatch S;Landen S;Moor AE;Brandis A;Giladi A;Avihail AS;David E;Amit I;Itzkovitz S
通讯作者：
Itzkovitz S
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
人肝肿瘤微环境的单个细胞地图集。
影响因子：
9.9
作者：
Massalha H;Bahar Halpern K;Abu-Gazala S;Jana T;Massasa EE;Moor AE;Buchauer L;Rozenberg M;Pikarsky E;Amit I;Zamir G;Itzkovitz S
通讯作者：
Itzkovitz S
DOI：
10.1056/nejmra1506330
发表时间：
2016-09-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Lazaridis KN;LaRusso NF
通讯作者：
LaRusso NF
影响因子：
48
作者：
Kiselev, Vladimir Yu;Yiu, Andrew;Hemberg, Martin
通讯作者：
Hemberg, Martin