Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes

Abstract

Inbred mice are a useful tool for studying the in vivo functions of platelets. Nonetheless, the mRNA signature of mouse platelets is not known. Here, we use pairedend next-generation RNA sequencing (RNA-seq) to characterize the polyadenylated transcriptomes of human and mouse platelets. We report that RNA-seq provides unprecedented resolution of mRNAs that are expressed across the entire human and mouse genomes. Transcript expression and abundance are often conserved between the 2 species. Several mRNAs, however, are differentially expressed in human and mouse platelets. Moreover, previously described functional disparities between mouse and human platelets are reflected in differences at the transcript level, including protease activated receptor-1, protease activated receptor-3, platelet activating factor receptor, and factor V. This suggests that RNA-seq is a useful tool for predicting differences in platelet function between mice and humans. Our nextgeneration sequencing analysis provides new insights into the human and murine platelet transcriptomes. The sequencing dataset will be useful in the design of mouse models of hemostasis and a catalyst for discovery of new functions of platelets. Access to the dataset is found in the "Introduction." (Blood. 2011; 118(14):e101-e111)

The TRPV1 ion channel is expressed in human but not mouse platelets

“…The anti-TRPV1 antibody used in this study was directed to the C-terminal of TRPV1, thus our data suggest the absence of all known murine TRPV1 isoforms from mouse platelets. Recent transcriptome profiles of murine and human platelets have demonstrated low levels of TRPV1 mRNA in human platelets, whilst it appeared to be absent from murine platelets [8], supporting our observations. These results demonstrate that murine platelets lack TRPV1, and thus cannot provide a model system in which to study the physiological function of TRPV1 in platelets in vivo.…”

“…The absence of TRPV1 from murine platelets adds to a growing body of evidence of differences in both the proteomes and transcriptomes of mouse and human platelets [8]. Thus, while platelets from genetically-modified mice provide a useful tool for an initial evaluation of the role of a variety of proteins in platelet function, caution must be exercised when extrapolating from mouse studies to consider human platelet function.…”

Measuring and interpreting platelet-leukocyte aggregates

“…10%–20% in human (26), and 1%–10% in mice (27–29). Furthermore, differences exist in receptor expression, with the most prominent being protease activated- and Fcγ receptors (30), hence also mechanisms of platelet activation might differ between mouse and human. Notably, however, the main receptors facilitating PLAs (i.e.…”

What Can Proteomics Tell Us About Platelets?

“…ACSA indicates acetyl-coenzyme A synthetase; DTS, dense tubular system; ER, endoplasmic reticulum; FG, fibrinogen, FN, fibronectin; GPVI, platelet glycoprotein VI; LAMP, lysosome-associated membrane glycoprotein; LDH, L-lactate dehydrogenase; MYH, myosin; PAR, proteinase-activated receptor; PDI, platelet disulfide isomerase; PF-4, platelet factor 4; SERCA, sarcoplasmic endoplasmic reticulum Ca human genes are expressed in platelets at the messenger RNA level. 68,69 Several studies focused on analysis of the platelet transcriptome [68][69][70][71][72] and some of these compared protein and transcript levels, deducing a certain degree of correlation. 68,70 A comprehensive comparison between our quantitative proteome data and published transcriptome data revealed only weak correlation.…”