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纵向多组学分析确定严重COVID-19轨迹的标志
作者:小柯机器人 发布时间:2020/11/29 21:59:44

德国基尔大学Philip Rosenstiel团队利用纵向多组学分析确定巨核细胞、红系细胞和成浆细胞的反应是严重COVID-19轨迹的标志。相关论文于2020年11月26日在线发表在《免疫》杂志上。

通过使用14名患者的两中心队列,研究人员进行了一项纵向多组学研究。研究人员分析了从最多5个时间点采集的外周血样本的整体转录组、整体DNA甲基化组和单细胞转录组(> 358,000个细胞,包括BCR谱)。在两个独立的COVID-19患者队列中进行了验证。严重的COVID-19的特征是增殖性代谢活跃的浆母细胞增加。
 
与重症疾病同时发生,研究人员还发现了IFN激活的循环巨核细胞的扩增和红细胞生成的增加以及缺氧信号的特征。巨核细胞和红细胞衍生的共表达模块可预测致命疾病的预后。这项研究证明了SARS-CoV-2感染对细胞的广泛作用超出了经典免疫细胞,并且可以作为开发COVID-19患者生物标志物和靶向治疗的切入点。
 
据了解,严重的COVID-19疾病轨迹相关细胞特征的时间分辨信息能够了解免疫反应的改变并寻找结局预测因子。
 
附:英文原文

Title: Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells and plasmablasts as hallmarks of severe COVID-19 trajectories

Author: Joana P. Bernardes, Neha Mishra, Florian Tran, Thomas Bahmer, Lena Best, Johanna I. Blase, Dora Bordoni, Jeanette Franzenburg, Ulf Geisen, Jonathan Josephs-Spaulding, Philipp Khler, Axel Künstner, Elisa Rosati, Anna C. Aschenbrenner, Petra Bacher, Nathan Baran, Teide Boysen, Burkhard Brandt, Niklas Bruse, Jonathan Drr, Andreas Drger, Gunnar Elke, David Ellinghaus, Julia Fischer, Michael Forster, Andre Franke, Sren Franzenburg, Norbert Frey, Anette Friedrichs, Janina Fu, Andreas Glück, Jacob Hamm, Finn Hinrichsen, Marc P. Hoeppner, Simon Imm, Ralf Junker, Sina Kaiser, Ying H. Kan, Rainer Knoll, Christoph Lange, Georg Laue, Clemens Lier, Matthias Lindner, Georgios Marinos, Robert Markewitz, Jacob Nattermann, Rainer Noth, Peter Pickkers, Klaus F. Rabe, Alina Renz, Christoph Rcken, Jan Rupp, Annika Schaffarzyk, Alexander Scheffold, Jonas Schulte-Schrepping, Domagoj Schunck, Dirk Skowasch, Thomas Ulas, Klaus-Peter Wandinger, Michael Wittig, Johannes Zimmermann, Hauke Busch, Bimba F. Hoyer, Christoph Kaleta, Jan Heyckendorf, Matthijs Kox, Jan Rybniker, Stefan Schreiber, Joachim Schultze, Philip Rosenstiel

Issue&Volume: 2020-11-26

Abstract: Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is required for understanding skewed immune responses and finding outcome predictors. Here, we performed a longitudinal multi-omics study using a two-centre cohort of 14 patients. We analysed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of IFN-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signalling. Megakaryocyte- and erythroid cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond classical immune cells and may serve as an entry point to develop biomarkers and targeted treatments of patients with COVID-19.

DOI: 10.1016/j.immuni.2020.11.017

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30504-5

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx