Megakaryocyte and Platelet Transcriptomics for Discoveries in Human Health and Disease

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2020 Apr 17

PMID 32295424

Citations 43

Authors

Pavel Davizon-Castillo

Jesse W Rowley

Matthew T Rondina

Affiliations

Soon will be listed here.

Abstract

Anucleate platelets, long viewed as merely cell fragments with a limited repertoire of rapid-acting hemostatic functions, are now recognized to have a complex and dynamic transcriptome mirroring that of many nucleated cells. The field of megakaryocyte and platelet transcriptomics has been rapidly growing, particularly with the advent of newer technologies such as next-generation RNA-sequencing. Studies interrogating the megakaryocyte and platelet transcriptome have led to a number of key insights into human health and disease. In this brief focused review, we will discuss some of the recent discoveries made through transcriptome analysis of megakaryocytes and platelets. We will also highlight the utility of integrating ribosome footprint analysis to augment discoveries. Both bulk and single-cell sequencing approaches will be reviewed, along with comparative studies between human and murine platelets under basal healthy settings and during acute systemic inflammatory diseases.

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References

Pellin D, Loperfido M, Baricordi C, Wolock S, Montepeloso A, Weinberg O . A comprehensive single cell transcriptional landscape of human hematopoietic progenitors. Nat Commun. 2019; 10(1):2395. PMC: 6546699. DOI: 10.1038/s41467-019-10291-0. View

Lood C, Amisten S, Gullstrand B, Jonsen A, Allhorn M, Truedsson L . Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease. Blood. 2010; 116(11):1951-7. DOI: 10.1182/blood-2010-03-274605. View

Campbell R, Franks Z, Bhatnagar A, Rowley J, Manne B, Supiano M . Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging. J Immunol. 2017; 200(1):295-304. PMC: 5736423. DOI: 10.4049/jimmunol.1700885. View

Ingolia N . Ribosome Footprint Profiling of Translation throughout the Genome. Cell. 2016; 165(1):22-33. PMC: 4917602. DOI: 10.1016/j.cell.2016.02.066. View

Chen G, Ning B, Shi T . Single-Cell RNA-Seq Technologies and Related Computational Data Analysis. Front Genet. 2019; 10:317. PMC: 6460256. DOI: 10.3389/fgene.2019.00317. View

Schubert S, Weyrich A, Rowley J . A tour through the transcriptional landscape of platelets. Blood. 2014; 124(4):493-502. PMC: 4110657. DOI: 10.1182/blood-2014-04-512756. View

Faraday N, Goldschmidt-Clermont P, Bray P . Gender differences in platelet GPIIb-IIIa activation. Thromb Haemost. 1997; 77(4):748-54. View

Rose J, Voora D, Cyr D, Lucas J, Zaas A, Woods C . Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction. PLoS One. 2015; 10(7):e0132259. PMC: 4507878. DOI: 10.1371/journal.pone.0132259. View

Simon L, Edelstein L, Nagalla S, Woodley A, Chen E, Kong X . Human platelet microRNA-mRNA networks associated with age and gender revealed by integrated plateletomics. Blood. 2014; 123(16):e37-45. PMC: 3990915. DOI: 10.1182/blood-2013-12-544692. View

10.

Heazlewood S, Williams B, Storan M, Nilsson S . The prospective isolation of viable, high ploidy megakaryocytes from adult murine bone marrow by fluorescence activated cell sorting. Methods Mol Biol. 2013; 1035:121-33. DOI: 10.1007/978-1-62703-508-8_10. View

11.

McDonald B, Dunbar M . Platelets and Intravascular Immunity: Guardians of the Vascular Space During Bloodstream Infections and Sepsis. Front Immunol. 2019; 10:2400. PMC: 6797619. DOI: 10.3389/fimmu.2019.02400. View

12.

Schwertz H, Koster S, Kahr W, Michetti N, Kraemer B, Weitz D . Anucleate platelets generate progeny. Blood. 2010; 115(18):3801-9. PMC: 2865870. DOI: 10.1182/blood-2009-08-239558. View

13.

de Oliveira Trugilho M, Hottz E, Brunoro G, Teixeira-Ferreira A, Carvalho P, Salazar G . Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue. PLoS Pathog. 2017; 13(5):e1006385. PMC: 5453622. DOI: 10.1371/journal.ppat.1006385. View

14.

Deppermann C, Kubes P . Start a fire, kill the bug: The role of platelets in inflammation and infection. Innate Immun. 2018; 24(6):335-348. PMC: 6830908. DOI: 10.1177/1753425918789255. View

15.

Tweeten K, Bulla Jr L, Consigli R . Characterization of an alkaline protease associated with a granulosis virus of Plodia interpunctella. J Virol. 1978; 26(3):703-11. PMC: 525894. View

16.

Guo L, Rondina M . The Era of Thromboinflammation: Platelets Are Dynamic Sensors and Effector Cells During Infectious Diseases. Front Immunol. 2019; 10:2204. PMC: 6753373. DOI: 10.3389/fimmu.2019.02204. View

17.

Armstrong P, Hoefer T, Knowles R, Tucker A, Hayman M, Ferreira P . Newly Formed Reticulated Platelets Undermine Pharmacokinetically Short-Lived Antiplatelet Therapies. Arterioscler Thromb Vasc Biol. 2017; 37(5):949-956. PMC: 5405774. DOI: 10.1161/ATVBAHA.116.308763. View

18.

Lu Y, Sanada C, Xavier-Ferrucio J, Wang L, Zhang P, Grimes H . The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification. Cell Rep. 2018; 25(11):3229. PMC: 6357951. DOI: 10.1016/j.celrep.2018.11.075. View

19.

Teruel-Montoya R, Kong X, Abraham S, Ma L, Kunapuli S, Holinstat M . MicroRNA expression differences in human hematopoietic cell lineages enable regulated transgene expression. PLoS One. 2014; 9(7):e102259. PMC: 4100820. DOI: 10.1371/journal.pone.0102259. View

20.

Marcantoni E, Allen N, Cambria M, Dann R, Cammer M, Lhakhang T . Platelet Transcriptome Profiling in HIV and ATP-Binding Cassette Subfamily C Member 4 (ABCC4) as a Mediator of Platelet Activity. JACC Basic Transl Sci. 2018; 3(1):9-22. PMC: 6058944. DOI: 10.1016/j.jacbts.2017.10.005. View