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Here, we investigated the regulatory role of platelets, that are easily and unlimitedly accessible and can modulate tissue regeneration. In co-cultures, platelets created a pro-stemness environment for neural stem\/progenitor cells (NSPCs) and enhanced the differentiation of oligodendrocyte progenitor cells. The effects were dependent on platelet numbers and the culture microenvironment, while the molecular signature of the NSPC response confirmed the role of Platelet-Derived Growth Factor and the upregulation of stemness-promoting genes. The same effects were exerted in vivo, but only when platelets were injected directly into the striatal parenchyma or were extravasated, in severely thrombocytopenic mice. In contrast, thrombocytopenia without platelet tissue-infiltration, in Nbeal2 knockout mice, did not affect the brain\u2019s progenitors. 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