Transcriptomic profiling of platelet senescence and platelet extracellular vesicles

Area of Science:

• Molecular Biology
• Cell Biology
• Genomics

Background:

• Platelets (PLTs) are crucial in vascular and neurological diseases, releasing platelet extracellular vesicles (PL-EVs).
• Senescent PLTs and PL-EVs accumulate in disease states.
• A comprehensive analysis of RNA in senescent PLTs and PL-EVs was lacking.

Purpose of the Study:

• To systematically analyze messenger RNA (mRNA) and microRNA (miRNA) composition in human platelets and PL-EVs during in vitro senescence.
• To investigate the potential role of RNA cargo in PLTs and PL-EVs in disease pathogenesis.

Main Methods:

• Isolation of PLTs and PL-EVs from stored human platelet concentrates on Days 0 and 5.
• Analysis of mRNA and miRNA species using microarrays and deep sequencing.
• Bioinformatic analysis for mRNA-miRNA correlations and miRNA target identification.

Main Results:

• In vitro platelet senescence led to decreased mRNA and increased miRNA species.
• Upregulated miRNAs in senescent PLTs and PL-EVs are associated with atherosclerosis, inflammation, and neurotransmission.
• PL-EVs showed enriched miRNAs linked to vascular, metabolic, and neurological disorders, including Alzheimer's disease targets.

Conclusions:

• Platelets degrade large RNA species during senescence while upregulating specific small RNAs.
• PL-EVs are enriched with disease-associated miRNAs, highlighting their role in vascular homeostasis.
• PL-EVs function as carriers of miRNA cargo relevant to neurodegenerative diseases.