小柯机器人

以色列魏茨曼科学研究所Eran Elinav和Ido Amit团队合作取得最新进展。他们发现急性肝衰竭（ALF）由MYC和微生物组依赖性程序调节。相关论文于2020年10月26日发表在《自然-医学》杂志上。

他们利用对乙酰氨基酚（APAP）和硫代乙酰胺（TAA）ALF模型来表征56,527个单细胞转录组，以定义小鼠ALF细胞图谱。他们证明独特的、以前未表征的星状细胞、内皮细胞、库普弗细胞，单核细胞和中性粒细胞图谱，以及它们复杂的细胞间串扰，驱动ALF。他们揭示了一个常见的MYC依赖性转录程序，在ALF期间协调星状、内皮和库普弗细胞的激活，这由肠道微生物组通过Toll样受体（TLR）信号传导来调节。

对MYC、上游TLR信号检查点或微生物组耗竭的药理抑制作用可抑制这种细胞特异性，并且依赖MYC程序，从而减弱ALF。在人体中，他们证明与健康供体相比，ALF移植受者的肝脏MYC表达上调。他们共同证明，详细的细胞/遗传解码可能使特定于途径的ALF治疗性干预成为可能。

据介绍，ALF是多种病因的暴发性并发症，其特征是快速的肝破坏，多器官衰竭和死亡。ALF的治疗主要限于支持治疗和肝移植。

附：英文原文

Title: Acute liver failure is regulated by MYC- and microbiome-dependent programs

Author: Aleksandra A. Kolodziejczyk, Sara Federici, Niv Zmora, Gayatree Mohapatra, Mally Dori-Bachash, Shanni Hornstein, Avner Leshem, Debby Reuveni, Ehud Zigmond, Ana Tobar, Tomer Meir Salame, Alon Harmelin, Amir Shlomai, Hagit Shapiro, Ido Amit, Eran Elinav

Issue&Volume: 2020-10-26

Abstract: Acute liver failure (ALF) is a fulminant complication of multiple etiologies, characterized by rapid hepatic destruction, multi-organ failure and mortality. ALF treatment is mainly limited to supportive care and liver transplantation. Here we utilize the acetaminophen (APAP) and thioacetamide (TAA) ALF models in characterizing 56,527 single-cell transcriptomes to define the mouse ALF cellular atlas. We demonstrate that unique, previously uncharacterized stellate cell, endothelial cell, Kupffer cell, monocyte and neutrophil subsets, and their intricate intercellular crosstalk, drive ALF. We unravel a common MYC-dependent transcriptional program orchestrating stellate, endothelial and Kupffer cell activation during ALF, which is regulated by the gut microbiome through Toll-like receptor (TLR) signaling. Pharmacological inhibition of MYC, upstream TLR signaling checkpoints or microbiome depletion suppress this cell-specific, MYC-dependent program, thereby attenuating ALF. In humans, we demonstrate upregulated hepatic MYC expression in ALF transplant recipients compared to healthy donors. Collectively we demonstrate that detailed cellular/genetic decoding may enable pathway-specific ALF therapeutic intervention. A single-cell map of transcriptomic changes during acute liver failure unveils new insights into pathogenesis and potential therapeutic targets.

DOI: 10.1038/s41591-020-1102-2

Source: https://www.nature.com/articles/s41591-020-1102-2

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
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