A spatial vascular transcriptomic, proteomic, and phosphoproteomic atlas unveils an angiocrine Tie-Wnt signaling axis in the liver.
A spatial vascular transcriptomic, proteomic, and phosphoproteomic atlas unveils an angiocrine Tie-Wnt signaling axis in the liver.
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DOI：
10.1016/j.devcel.2021.05.001
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发表时间：
2021-06-07
影响因子：
11.8
通讯作者：
Augustin HG
中科院分区：
文献类型：
--
作者：
Inverso D;Shi J;Lee KH;Jakab M;Ben-Moshe S;Kulkarni SR;Schneider M;Wang G;Komeili M;Vélez PA;Riedel M;Spegg C;Ruppert T;Schaeffer-Reiss C;Helm D;Singh I;Boutros M;Chintharlapalli S;Heikenwalder M;Itzkovitz S;Augustin HG
单细胞转录组学（scRNA-seq）彻底改变了对组织结构和功能的空间结构的理解。推进scRNA-seq分析的“以转录物为中心”的观点目前受到蛋白质组学和全基因组技术分析翻译后修饰的有限分辨率的限制。在这里，通过将空间细胞分选与转录组学和定量蛋白质组学/磷酸化蛋白质组学相结合，我们建立了肝内皮的空间分辨蛋白质组景观，对带状血管信号传导机制产生了深刻的机械见解。受体酪氨酸激酶的磷酸化检测优先在中央静脉区域，导致非典型的酪氨酸磷酸化富集。原型生物学验证将Tie受体信号传导鉴定为血管Wnt活性的选择性和特异性调节剂，其协调血管分泌信号传导，从而在肝再生期间控制肝细胞功能。总之，这项研究对肝内皮细胞信号传导的空间组织产生了基本的见解。空间分选可以用作scRNA-seq限定的细胞（亚）群的多组学分析的通用适应策略。ScRNA-seq引导的空间分选使得能够对肝脏脉管系统进行多组解剖肝脏窦状内皮细胞具有混合血管-淋巴表型内皮细胞分子的酪氨酸磷酸化在中央静脉上富集内皮Tie 1形状肝脏Wnt信号分区并促进肝脏再生Inverso，Shi et al.生成具有转录组、蛋白质组和磷酸化蛋白质组空间分辨率的肝内皮细胞（L-EC）的多组百科全书。该研究提供了对肝脏血管分区的深入了解，并为scRNA-seq-data引导的空间蛋白质组和磷酸化蛋白质组分析提供了模板。
Single-cell transcriptomics (scRNA-seq) has revolutionized the understanding of the spatial architecture of tissue structure and function. Advancing the “transcript-centric” view of scRNA-seq analyses is presently restricted by the limited resolution of proteomics and genome-wide techniques to analyze post-translational modifications. Here, by combining spatial cell sorting with transcriptomics and quantitative proteomics/phosphoproteomics, we established the spatially resolved proteome landscape of the liver endothelium, yielding deep mechanistic insight into zonated vascular signaling mechanisms. Phosphorylation of receptor tyrosine kinases was detected preferentially in the central vein area, resulting in an atypical enrichment of tyrosine phosphorylation. Prototypic biological validation identified Tie receptor signaling as a selective and specific regulator of vascular Wnt activity orchestrating angiocrine signaling, thereby controlling hepatocyte function during liver regeneration. Taken together, the study has yielded fundamental insight into the spatial organization of liver endothelial cell signaling. Spatial sorting may be employed as a universally adaptable strategy for multiomic analyses of scRNA-seq-defined cellular (sub)-populations. ScRNA-seq-guided spatial sort enables multiomic dissection of the liver vasculature Liver sinusoidal endothelial cells have a hybrid vascular-lymphatic phenotype Tyrosine phosphorylation of endothelial cell molecules is enriched on central vein Endothelial Tie1 shapes hepatic Wnt signal zonation and promotes liver regeneration Inverso, Shi et al. generate a multiomic encyclopedia of liver endothelial cells (L-ECs) with spatial resolution of transcriptome, proteome, and phosphoproteome. The study provides insight into liver vascular zonation and a template for scRNA-seq-data-guided spatial proteome and phosphoproteome analyses.
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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：
64.5
作者：
Huttlin EL;Jedrychowski MP;Elias JE;Goswami T;Rad R;Beausoleil SA;Villén J;Haas W;Sowa ME;Gygi SP
通讯作者：
Gygi SP
影响因子：
64.8
作者：
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影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
15.9
作者：
Kim, Minah;Allen, Breanna;McDonald, Donald M.
通讯作者：
McDonald, Donald M.