Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis.
Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis.
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DOI：
10.1038/s41598-022-16754-7
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发表时间：
2022-08-05
影响因子：
4.6
通讯作者：
Pers, Tune H.
中科院分区：
文献类型：
--
作者：
Fred, Rikard G.;Pedersen, Julie Steen;Thompson, Jonatan J.;Lee, Julie;Timshel, Pascal N.;Stender, Stefan;Rygg, Marte Opseth;Gluud, Lise Lotte;Kristiansen, Viggo Bjerregaard;Bendtsen, Flemming;Hansen, Torben;Pers, Tune H.
这项研究的目的是表征非酒精性脂肪性肝炎(NASH)的细胞类型特异性转录信号，以提高我们对该疾病的理解。我们对10例NASH患者的肝活检组织进行了单细胞RNA测序。我们应用加权基因共表达网络分析，并使用公开可用的RNA测序数据集验证了我们的发现，该数据来自160名非酒精性脂肪性肝病(NAFLD)患者和24名肝脏组织学正常的对照组。我们的研究提供了人类NASH病理的全面单细胞分析，描述了19627例经活检证实的NASH患者的单细胞转录本。我们的数据表明，以前的“NASH相关巨噬细胞”的概念可以通过上调正常存在的肝巨噬细胞亚群来解释。同样，我们描述了与纤维化水平相关的两种不同的活化肝星状细胞群。最后，我们发现NAFLD的几个循环标志物在肝细胞中的表达与NAFLD全基因组关联研究(GWAS)预测的效应基因一起在肝细胞中共同调节，并与补体系统的异常相结合。总之，我们的单细胞转录数据集提供了对与炎症和纤维化相关的新的细胞类型特定和一般生物过程的见解，强调了研究人类NASH细胞类型特定生物过程的重要性。
The aim of this study is to characterize cell type-specific transcriptional signatures in non-alcoholic steatohepatitis (NASH) to improve our understanding of the disease. We performed single-cell RNA sequencing on liver biopsies from 10 patients with NASH. We applied weighted gene co-expression network analysis and validated our findings using a publicly available RNA sequencing data set derived from 160 patients with non-alcoholic fatty liver disease (NAFLD) and 24 controls with normal liver histology. Our study provides a comprehensive single-cell analysis of NASH pathology in humans, describing 19,627 single-cell transcriptomes from biopsy-proven NASH patients. Our data suggest that the previous notion of ”NASH-associated macrophages” can be explained by an up-regulation of normally existing subpopulations of liver macrophages. Similarly, we describe two distinct populations of activated hepatic stellate cells, associated with the level of fibrosis. Finally, we find that the expression of several circulating markers of NAFLD are co-regulated in hepatocytes together with predicted effector genes from NAFLD genome-wide association studies (GWAS), coupled to abnormalities in the complement system. In sum, our single-cell transcriptomic data set provides insights into novel cell type-specific and general biological processes associated with inflammation and fibrosis, emphasizing the importance of studying cell type-specific biological processes in human NASH.
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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
DOI：
10.1002/hep.31215
发表时间：
2020-12
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Terkelsen MK;Bendixen SM;Hansen D;Scott EAH;Moeller AF;Nielsen R;Mandrup S;Schlosser A;Andersen TL;Sorensen GL;Krag A;Natarajan KN;Detlefsen S;Dimke H;Ravnskjaer K
通讯作者：
Ravnskjaer K
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：
24.5
作者：
Krenkel, Oliver;Hundertmark, Jana;Tacke, Frank
通讯作者：
Tacke, Frank
影响因子：
4.1
作者：
ARENZANA, N;DECORDOBA, SR;REYCAMPOS, J
通讯作者：
REYCAMPOS, J