Genomics and transcriptomics of megakaryocytes and platelets: Implications for health and disease

Fisher, Marlie H; Paola, Jorge Di

doi:10.1002/rth2.12129

Cited by 15 publications

(19 citation statements)

References 98 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The study of RNA sorting during platelet biogenesis and of the modulating influence of miRNA is also important. 149 Despite current technological advances, a high proportion of new cases of inherited thrombocytopenia remain without diagnosis; this proportion is often estimated to be around 50% but can be as high as 70% or more depending on the extent to which patients with easily identified disorders have been prescreened. 127 , 128 , 150 , 151 Assigning a significance to the variants is key, because in the absence of confirmation with follow-up biological studies, including the use of mouse, zebrafish or Drosophila models or site-directed mutagenesis in megakaryocyte-related cells, the alternative is to use sophisticated bioinformatics; new variants are being variously graded as highly significant and likely pathogenic to those of unknown significance.…”

Section: Perspectivesmentioning

confidence: 99%

Inherited thrombocytopenias: history, advances and perspectives

Nurden

2020

Haematologica

View full text Add to dashboard Cite

In the late 19 th century improvements to the light microscope led to anucleate platelets being visualized in great numbers in human blood. Early pioneers in the field of platelet research included the Canadian William Osler, a Paris hematologist, George Hayem, who performed the first accurate platelet count, and the Italian Giulio Bizzozero. 1 In 1906, James Homer Wright confirmed that platelets were produced by bone marrow megakaryocytes. 2 When, in 1951, Harrington et al. 3 observed purpura in a child of a mother with immune thrombocytopenic purpura, a maternal factor was said to be destroying the platelets. Anti-platelet antibodies were identified as the cause and platelet transfusions, immunosuppressive therapy and splenectomy became standard treatments. Acquired thrombocytopenia, often with defective platelet function, has many causes. For example, it may be an immune response linked to blood transfusions and drugs, a direct consequence of viral or bacterial infections, be the result of other hematologic disorders or be secondary to many major illnesses. However, some thrombocytopenias are inherited and Professors Jean Bernard and Jean-Pierre Soulier in Paris were pioneers in this domain, describing in 1948 what they called in French "dystrophie thrombocytaire hémorragipare congénitale", later renamed the Bernard-Soulier syndrome (BSS). 4 Strikingly, many platelets were enlarged and some were giant. A key to the molecular defect was the platelet deficit of sialic acid, a negatively charged monosaccharide terminating many of the oligosaccharides of platelet glycoproteins (GP) and

show abstract

Section: Perspectivesmentioning

confidence: 99%

Inherited thrombocytopenias: history, advances and perspectives

Nurden

2020

Haematologica

View full text Add to dashboard Cite

show abstract

“…Therefore, platelets have high versatility and adaptability in structure and function, and the platelet transcriptome has a relevant role in mediating platelet function in health and disease [ 3 , 13 , 14 ]. Multiple mutations associated with defects of platelet function have been identified in genes encoding receptors, intracellular signaling proteins, cytoskeletal proteins, and proteins regulating the biogenesis of platelet granules [ 3 , 15 , 16 ].…”

Section: Platelet Biology and Its Roles In Human Diseasesmentioning

confidence: 99%

Platelets in Healthy and Disease States: From Biomarkers Discovery to Drug Targets Identification by Proteomics

Gianazza

Brioschi

Baetta

et al. 2020

IJMS

View full text Add to dashboard Cite

Platelets are a heterogeneous small anucleate blood cell population with a central role both in physiological haemostasis and in pathological states, spanning from thrombosis to inflammation, and cancer. Recent advances in proteomic studies provided additional important information concerning the platelet biology and the response of platelets to several pathophysiological pathways. Platelets circulate systemically and can be easily isolated from human samples, making proteomic application very interesting for characterizing the complexity of platelet functions in health and disease as well as for identifying and quantifying potential platelet proteins as biomarkers and novel antiplatelet therapeutic targets. To date, the highly dynamic protein content of platelets has been studied in resting and activated platelets, and several subproteomes have been characterized including platelet-derived microparticles, platelet granules, platelet releasates, platelet membrane proteins, and specific platelet post-translational modifications. In this review, a critical overview is provided on principal platelet proteomic studies focused on platelet biology from signaling to granules content, platelet proteome changes in several diseases, and the impact of drugs on platelet functions. Moreover, recent advances in quantitative platelet proteomics are discussed, emphasizing the importance of targeted quantification methods for more precise, robust and accurate quantification of selected proteins, which might be used as biomarkers for disease diagnosis, prognosis and therapy, and their strong clinical impact in the near future.

show abstract

“…[ 26 ] PRP has been more commonly used to treat non‐cicatricial alopecia, particularly AGA, [ 7 ] but is more recently being used in patients with cicatricial alopecia. [ 27 ] Since the transcriptional signature and protein secretion profile in platelets are related to megakaryocyte gene expression that is altered during an ongoing inflammatory condition, [ 28 ] we tested whether GF secretion by platelets was distinct between non‐cicatricial and cicatricial alopecia patients. We did not observe any significant difference in GF secretion by platelets in PRP of patients based on their alopecia diagnosis (Figure 2) suggesting that the variability noticed when all patient samples were pooled is not related to the type of alopecia diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in amount of growth factors secreted by platelets in platelet‐rich plasma samples from alopecia patients

Shaik

Estharabadi

Farah

et al. 2020

Experimental Dermatology

View full text Add to dashboard Cite

Platelet α‐granules release growth factors (GFs) that promote healing and tissue regeneration. Platelet‐rich plasma (PRP) is shown to be beneficial in treating alopecia, and however, clinical response can be inconsistent. Due to several fold enrichment of platelets secreting large quantities of GFs following PRP injections, heterogeneity in amounts of GFs secreted by platelets may contribute to inconsistent clinical responses. Herein, we evaluated factors that could potentially contribute to heterogeneous secretion of GFs by platelets. We measured platelet secretion of transforming growth factor beta1 (TGFβ1), platelet‐derived growth factor (PDGF‐BB), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF2) in aliquots of de‐identified PRP samples from female patients undergoing therapy in the hair disease clinic. Although secretion of GFs by platelets was comparable in PRP samples of patients with non‐cicatricial and cicatricial alopecia, a Shapiro‐Wilk test for normal distribution indicated significant variability across all patient samples. The amount of GF secreted by platelets was comparable when PRP prepared from two FDA‐cleared devices with distinct techniques were compared. We provide evidence of platelets secreting heterogeneous amounts of GFs within each sample as high and low secretion of random factors could be simultaneously detected. These results suggest inherent heterogeneity in secretion of GFs by platelets in patient samples that are not influenced by the device used to prepare PRP. Since some GFs could have antagonistic effects on hair growth, a balance between amounts of growth promoting and inhibiting factors may be crucial in determining clinical response to PRP therapy.

show abstract

Genomics and transcriptomics of megakaryocytes and platelets: Implications for health and disease

Cited by 15 publications

References 98 publications

Inherited thrombocytopenias: history, advances and perspectives

Inherited thrombocytopenias: history, advances and perspectives

Platelets in Healthy and Disease States: From Biomarkers Discovery to Drug Targets Identification by Proteomics

Heterogeneity in amount of growth factors secreted by platelets in platelet‐rich plasma samples from alopecia patients

Contact Info

Product

Resources

About