Enhanced regenerative and developmental potential of embryonal and stem cell-derived platelets compared to adult platelets.

The molecular features and multifaceted roles of platelets have been well characterized in adult mammals, but little is known about platelets at earlier developmental stages. In this study, we conduct transcriptomic and proteomic profiling of mouse embryonic platelets and find that, compared to adult platelets, they exhibit reduced classic immune-regulatory and procoagulant features but enhanced development-supporting traits. Notably, embryonic platelets interact more robustly with various cell types, including fibroblasts, and significantly accelerate refractory wound healing. Mechanistically, embryonic platelets promote fibroblast proliferation by releasing higher levels of IGF2. We also identify a CD59(a)(+) platelet subpopulation in adult mice and humans that mimics the function of embryonic platelets. Additionally, human induced pluripotent stem cell (iPSC)-derived platelets share similar molecular and functional properties with embryonic platelets. Our findings highlight the unique multi-omics signatures and superior regenerative potential of embryonic and human induced pluripotent stem cell (hiPSC)-derived platelets, offering promising directions for tailoring platelet-based therapies to specific clinical needs.