The First Comprehensive Description of the Platelet Single Cell Transcriptome

Platelets are derived from megakaryocytes, either in peripheral or pulmonic circulation. The transcriptome of megakaryocytes has been studied, while the platelet transcriptome is thought to be a reflection of their parent cells; it has not yet been investigated. Although platelets lack nuclei, they inherit RNA from their parent megakaryocytes, while only about 10% of them are believed to contain enough RNA for meaningful analysis. This study explores the potential of single-cell RNA sequencing to analyze the platelet transcriptome, aiming to expand our understanding of platelets beyond their traditional role in coagulation. Using acridine orange staining and antibody-based sequencing, we successfully sequenced RNA from seven healthy donors. Results revealed significant heterogeneity in gene expression, with common platelet markers, such as ITGA2B and GP1B, being less abundant than expected. Interestingly, immune markers associated with lung megakaryocytes were not strongly represented in peripheral platelets. Comparison with current algorithms for cell identification suggests that platelets are often misclassified as other blood cell types, highlighting limitations of existing pipelines in platelet annotation. This misclassification may have led to misrepresentation of platelet transcriptomics in previous studies. These findings underscore the need for tailored sequencing methods to accurately profile platelets and set the foundation for further exploration of platelet biology and immune function, potentially opening avenues for therapeutic interventions in immune modulation, drug delivery, and the use of platelets as disease biomarkers in cancer and other conditions.