Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits

The hemostatic process relies on platelet and coagulation activation, with additional roles of red blood cells and the vessel wall. By systematic screening of databases for gene-linked information on hemostasis, we collected phenotypic profiles of 3474 orthologous human and mouse genes regarding bleeding, arterial thrombosis, thrombophilia, platelet traits, coagulation, and erythrocytes. Comparisons showed that defects in 252 mouse genes led to increased bleeding combined with platelet dysfunction or thrombocytopenia, in addition to 150 human orthologs that are registered for familial bleeding disorders, based on panel sequencing. Additionally, 139 mouse genes contributed to arterial thrombosis without bleeding phenotype. To further investigate the role of platelets in hemostasis, we integrated multiple genome-wide RNA-sequencing transcriptomes and proteomes from healthy subjects and C57BL/6 mice. This provided reference levels for 54 790 (54 247) transcripts and 6379 (4563) proteins in human (mouse) platelets. Orthologous transcripts in human and mouse platelets correlated with <i>R=</i>0.75, whereas orthologous platelet proteins correlated with <i>R=</i>0.87. Comparison with the phenotypic analysis revealed the following: (i) overall high qualitative similarity of human and mouse platelets regarding composition and function; (ii) presence of transcripts in platelets for most of the 3474 phenotyped genes; (iii) preponderance of syndromic platelet-expressed genes; and (iv) 20-40% overlap with genes from genome-wide association studies. For 42 mouse genes, among which receptors, signaling proteins, and transcription regulators (ASXL1, ERG, GATA2, MEIS1, NFE2, and TAL1), we confirmed novel links with human platelet function or count. This interspecies comparison can serve as a valuable resource for researchers and clinicians studying the genetics of blood-borne hemostasis and thrombosis.

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Publication Details

Journal
Blood Vessels Thrombosis & Hemostasis
Published
2025-03-28
DOI
https://doi.org/10.1016/j.bvth.2025.100068
Citations
4
Primary Topic
Platelet Disorders and Treatments
Type
article
Field-Weighted Citation Impact
7.08

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article

Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits

Fiorella A. Solari, Neil V. Morgan, Wolfram Ruf, Matthew T. Rondina et al.
4 citations
Blood Vessels Thrombosis & Hemostasis
Platelet Disorders and Treatments
7.08
article

Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits

Fiorella A. Solari, Neil V. Morgan, Wolfram Ruf, Matthew T. Rondina, Isabella Provenzale, Johan W. M. Heemskerk, Albert Sickmann, Ilaria De Simone, Carina Santos, Saskia E.M. Schols, Elizabeth A. Middleton, Sarah K. Westbury, Mattia Frontini, Bas de Laat, Luigi Grassi, Jingnan Huang, Fédérico Marini, Kunpeng Li, Frauke Swieringa, Xiang Gui
article en
4 citations

Abstract

The hemostatic process relies on platelet and coagulation activation, with additional roles of red blood cells and the vessel wall. By systematic screening of databases for gene-linked information on hemostasis, we collected phenotypic profiles of 3474 orthologous human and mouse genes regarding bleeding, arterial thrombosis, thrombophilia, platelet traits, coagulation, and erythrocytes. Comparisons showed that defects in 252 mouse genes led to increased bleeding combined with platelet dysfunction or thrombocytopenia, in addition to 150 human orthologs that are registered for familial bleeding disorders, based on panel sequencing. Additionally, 139 mouse genes contributed to arterial thrombosis without bleeding phenotype. To further investigate the role of platelets in hemostasis, we integrated multiple genome-wide RNA-sequencing transcriptomes and proteomes from healthy subjects and C57BL/6 mice. This provided reference levels for 54 790 (54 247) transcripts and 6379 (4563) proteins in human (mouse) platelets. Orthologous transcripts in human and mouse platelets correlated with <i>R=</i>0.75, whereas orthologous platelet proteins correlated with <i>R=</i>0.87. Comparison with the phenotypic analysis revealed the following: (i) overall high qualitative similarity of human and mouse platelets regarding composition and function; (ii) presence of transcripts in platelets for most of the 3474 phenotyped genes; (iii) preponderance of syndromic platelet-expressed genes; and (iv) 20-40% overlap with genes from genome-wide association studies. For 42 mouse genes, among which receptors, signaling proteins, and transcription regulators (ASXL1, ERG, GATA2, MEIS1, NFE2, and TAL1), we confirmed novel links with human platelet function or count. This interspecies comparison can serve as a valuable resource for researchers and clinicians studying the genetics of blood-borne hemostasis and thrombosis.

Blood Vessels Thrombosis & HemostasisVol. 2(3)
National Health Service (GB), Radboud University Nijmegen (NL), Johannes Gutenberg University Mainz (DE), University of Utah (US), University of Exeter (GB), University of Cambridge (GB), Radboud University Medical Center (NL), Southern University of Science and Technology (CN), Maastricht University (NL), University of Bristol (GB), University Medical Center of the Johannes Gutenberg University Mainz (DE), Leibniz Institute for Analytical Sciences - ISAS (DE), NIHR Exeter Clinical Research Facility (GB), Synapse (Netherlands) (NL), George E. Wahlen Department of VA Medical Center (US), University of Birmingham (GB), Ruhr University Bochum (DE)
National Institute for Health and Care Research, British Heart Foundation, Department of Health and Social Care, European Commission, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, China Scholarship Council
Zero hunger
Openalex Percentile: Top 3%
Platelet Disorders and Treatments
7.08
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