Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function

Goodall, Alison H.; Burns, Philippa; Salles, Isabelle I.; Macaulay, Iain C.; Jones, Chris I.; Ardissino, Diego; Bono, Bernard de; Bray, Sarah; Deckmyn, Hans; Dudbridge, Frank; Fitzgerald, Desmond J.; Garner, Stephen F.; Gusnanto, Arief; Koch, Kerstin; Langford, Cordelia; O’Connor, Marie; Rice, Catherine M.; Stemple, Derek L.; Stephens, Jonathan; Trip, Mieke D.; Zwaginga, Jaap‐Jan; Samani, Nilesh J.; Watkins, Nicholas A.; Maguire, Patricia B.; Ouwehand, Willem H.

doi:10.1182/blood-2010-04-280925

Cited by 90 publications

(84 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These molecules in platelets may come from different sources, such as those inherited from megakaryocytes, those absorbed from the plasma, or those generated de novo. With regard to de novo synthesis of molecules in platelets, although platelets are anucleate, they express significant amounts of RNA, including mRNAs (e.g., premature and mature RNA), structural and catalytic RNAs (e.g., ribosomal and tRNA), regulatory RNAs (e.g., microRNA), and noncoding RNA (e.g., anti-sense RNA) (90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105). More recently, it also was revealed that platelets contain all of the molecular machinery to translate mRNA into proteins, and they have the ability to transfer RNA to recipient cells where it can regulate cellular function (101-104).…”

Section: Platelet Transcriptomicsmentioning

confidence: 99%

Nouvelle Cuisine: Platelets Served with Inflammation

Kapur

Zufferey

Boilard

et al. 2015

The Journal of Immunology

179

191

View full text Add to dashboard Cite

Platelets are small cellular fragments with the primary physiological role of maintaining hemostasis. In addition to this well-described classical function, it is becoming increasingly clear that platelets have an intimate connection with infection and inflammation. This stems from several platelet characteristics, including their ability to bind infectious agents and secrete many immunomodulatory cytokines and chemokines, as well as their expression of receptors for various immune effector and regulatory functions, such as TLRs, which allow them to sense pathogen-associated molecular patterns. Furthermore, platelets contain RNA that can be nascently translated under different environmental stresses, and they are able to release membrane microparticles that can transport inflammatory cargo to inflammatory cells. Interestingly, acute infections can also result in platelet breakdown and thrombocytopenia. This report highlights these relatively new aspects of platelets and, thus, their nonhemostatic nature in an inflammatory setting.

show abstract

Section: Platelet Transcriptomicsmentioning

confidence: 99%

Nouvelle Cuisine: Platelets Served with Inflammation

Kapur

Zufferey

Boilard

et al. 2015

The Journal of Immunology

179

191

View full text Add to dashboard Cite

show abstract

“…Because platelets do not contain a nucleus, their RNA transcripts, needed for functional maintenance, are derived from megakaryocytes during platelet origination. 6,8,9 Platelet RNA can be readily isolated and subjected to gene-expression analysis. [8][9][10] Here we show that blood platelets take up tumor-derived secreted membrane vesicles that can contain tumor-associated RNA and that platelets can serve as a potential biomarker source for cancer diagnostics.…”

Section: Introductionmentioning

confidence: 99%

Blood platelets contain tumor-derived RNA biomarkers

Nilsson

Balaj

Hulleman

et al. 2011

Blood

331

302

View full text Add to dashboard Cite

Diagnostic platforms providing biomarkers that are highly predictive for diagnosing, monitoring, and stratifying cancer patients are key instruments in the development of personalized medicine. We demonstrate that tumor cells transfer (mutant) RNA into blood platelets in vitro and in vivo, and show that blood platelets isolated from glioma and prostate cancer patients contain the cancer-associated RNA biomarkers EGFRvIII and PCA3, respectively. In addition, gene-expression profiling revealed a distinct RNA signature in platelets from glioma patients compared with normal control subjects. Because platelets are easily accessible and isolated, they may form an attractive platform for the companion diagnostics of cancer. (Blood. 2011;118(13):3680-3683)

show abstract

“…[1][2][3][4][5] As part of this effort, we previously identified a panel of platelet membrane proteins that were expressed more highly in MKs and resting endothelial cells (ECs) than in other blood cell lineages, but with hitherto unknown roles in platelet function or thrombus formation. 6 Of the 279 genes identified, 4 (including bone morphogenetic protein and activin membrane-bound inhibitor [BAMBI]) were selected for functional analysis in zebrafish.…”

Section: Introductionmentioning

confidence: 99%

Vessel wall BAMBI contributes to hemostasis and thrombus stability

Salles‐Crawley

Monkman

Ahnström

et al. 2014

Blood

View full text Add to dashboard Cite

Key Points• This is the first report to describe the influence of BAMBI on both hemostasis and thrombus stability.• BAMBI present in the blood vessel wall (most likely the endothelium) rather than platelet BAMBI is required for thrombus stability.Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is a transmembrane protein related to the transforming growth factor-b superfamily, and is highly expressed in platelets and endothelial cells. We previously demonstrated its positive role in thrombus formation using a zebrafish thrombosis model. In the present study, we used Bambi-deficient mice and radiation chimeras to evaluate the function of this receptor in the regulation of both hemostasis and thrombosis. We show that Bambi 2/2 and Bambi 1/2 mice exhibit mildly prolonged bleeding times compared with Bambi 1/1 littermates. In addition, using 2 in vivo thrombosis models in mesenterium or cremaster muscle arterioles, we demonstrate that Bambi-deficient mice form unstable thrombi compared with Bambi 1/1 mice. No defects in thrombin generation in Bambi 2/2 mouse plasma could be detected ex vivo. Moreover, the absence of BAMBI had no effect on platelet counts, platelet activation, aggregation, or platelet procoagulant function. Similar to Bambi 2/2 mice, Bambitransplanted with Bambi 1/1 bone marrow formed unstable thrombi in the laser-induced thrombosis model that receded more rapidly than thrombi that formed in Bambi 1/1 mice receiving Bambi 2/2 bone marrow transplants.Taken together, these results provide strong evidence for an important role of endothelium rather than platelet BAMBI as a positive regulator of both thrombus formation and stability. (Blood. 2014;123(18):2873-2881

show abstract

Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function

Cited by 90 publications

References 44 publications

Nouvelle Cuisine: Platelets Served with Inflammation

Nouvelle Cuisine: Platelets Served with Inflammation

Blood platelets contain tumor-derived RNA biomarkers

Vessel wall BAMBI contributes to hemostasis and thrombus stability

Contact Info

Product

Resources

About