A Multi-Omics Approach Reveals Novel Regulators of Plasma Factor V Levels: highlight on CLEC4M as a Clearance Receptor.

IF 21 1区医学 Q1 HEMATOLOGY

Blood Pub Date : 2025-05-13 DOI:10.1182/blood.2024027006

Gaëlle Munsch,Adarsh Mohapatra,Astrid van Hylckama Vlieg,Marcus E Kleber,Angel Martinez-Perez,Ngoc-Quynh Le,Kristian Dalsbø Hindberg,Philip J Dusart,Marine Germain,Florian Thibord,Jean-François Deleuze,Graciela E Delgado,Louisa Goumidi,Pierre Suchon,Noémie Saut,Juan Carlos Souto,Lynn Butler,Jose Manuel Soria,John-Bjarne Hansen,Winfried März,Frits R Rosendaal,Elisabetta Castoldi,Franck Peiretti,Maria Sabater-Lleal,David-Alexandre Tregouet,Pierre-Emmanuel Morange

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Abstract

Coagulation factor V (FV) is a key protein in maintaining the hemostatic balance, with abnormal plasma levels associated with both thrombotic and hemorrhagic conditions. We propose a comprehensive bioinformatic analysis integrating large scale proteogenomics and transcriptomic data from original and public datasets. We identify a biological fingerprint of 26 new proteins and loci involved in the regulation of plasma FV levels. Furthermore, the mRNA expression levels of 10 of these components show strong correlation in liver. In addition, we provide experimental evidence for the involvement of one of the newly identified players (CLEC4M) in the clearance of FV. This work opens new avenues for a better understanding of the physiological processes involved in thrombotic and bleeding disorders.

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多组学方法揭示血浆因子V水平的新调节因子：重点关注CLEC4M作为清除受体。

凝血因子V （FV）是维持止血平衡的关键蛋白，异常血浆水平与血栓和出血状况相关。我们提出一个全面的生物信息学分析整合大规模的蛋白质基因组学和转录组学数据从原始和公共数据集。我们鉴定了26个参与血浆FV水平调节的新蛋白和位点的生物指纹。此外，其中10种成分的mRNA表达水平在肝脏中表现出很强的相关性。此外，我们还提供了实验证据，证明新发现的一种参与者（CLEC4M）参与了FV的清除。这项工作为更好地理解血栓性和出血性疾病的生理过程开辟了新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Blood 医学-血液学

CiteScore

23.60

自引率

3.90%

发文量

955

审稿时长

1 months

期刊介绍： Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.