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肝癌癌胚内皮细胞重编程促进免疫抑制性巨噬细

时间:2020-09-26 18:59 作者:直播平台竞猜 点击:

本期文章:《细胞》:Online/在线发表

新加坡基因研究院Ramanuj DasGupta、Ankur Sharma、Florent Ginhoux和新加坡国家癌症中心Pierce K.H. Chow研究组合作的新研究,揭示了肝癌癌胚内皮细胞重编程促进免疫抑制性巨噬细胞的产生。相关论文在线发表在2020年9月24日出版的《细胞》杂志上。

研究人员利用scRNA测序表征了人类肝脏细胞从发育到疾病的图谱。对人类胎儿、肝细胞癌(HCC)和小鼠肝脏约212,000个代表性细胞进行的分析表明,肿瘤微环境具有明显的胎儿样重编程。具体来说,HCC发育的特征让人联想到胎儿的发育,包括胎儿相关内皮细胞(PLVAP /VEGFR2)和胎儿样(FOLR2)肿瘤相关巨噬细胞的重新出现。跨物种比较分析表明小鼠胚胎、胎儿肝脏和肿瘤巨噬细胞之间存在相似性。

空间转录组学进一步表明胎儿的肝脏和肝癌之间存在共享的胎儿生态系统。此外,基因调控分析、空间转录组学和体外功能测定均暗示了VEGF和NOTCH信号传导在维持胎儿生态系统中的作用。总之,胎儿肝脏和肝癌细胞共享免疫抑制的癌胎生态系统。

该研究结果揭示了肿瘤生态系统中之前未报道的癌胎重编程方法,为肝癌的治疗干预提供了新的靶点,并为鉴定其他癌症和疾病提供了借鉴。

附:英文原文

 

Title:Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma

 

Author:Ankur Sharma Justine Jia Wen Seow 15 Charles-Antoine Dutertre 15 Pierce K.H. Chow Florent Ginhoux Ramanuj DasGupta 16

 

Issue&Volume:September 24, 2020

 

Abstract: We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of ∼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal-like reprogramming of the tumor microenvironment. Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including re-emergence of fetal-associated endothelial cells (PLVAP/VEGFR2) and fetal-like (FOLR2) tumor-associated macrophages. In a cross-species comparative analysis, we discovered remarkable similarity between mouse embryonic, fetal-liver, and tumor macrophages. Spatial transcriptomics further revealed a shared onco-fetal ecosystem between fetal liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem in fetal liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease.

 

DOI:https://doi.org/10.1016/j.cell.2020.08.040

 

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31082-5

期刊信息

Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216

官方网址:https://www.cell.com/

投稿链接:https://www.editorialmanager.com/cell/default.aspx