Siglec-7 Links Mitochondrial Dynamics to Megakaryocytic Differentiation

Abstract

Platelet biogenesis begins with the differentiation of hematopoietic stem cells (HSCs) into megakaryocytes (MKs) in the bone marrow, where mature MKs undergo endomitosis and ultimately release platelets. This program is tightly regulated by thrombopoietin, transcription factors, and metabolic cues, including mitochondrial reactive oxygen species and mitochondrial dynamics, which are now recognized as key drivers of megakaryopoiesis and thrombopoiesis. Sialic acid-binding immunoglobulin-like lectin (Siglec-7), a glycan-recognizing receptor, has been linked to mitochondrial dysfunction in natural killer cells, suggesting a potential role in modulating effector functions through oxidative phosphorylation. Here, using a phorbol 12-myristate 13-acetate (PMA)-induced K562 MK differentiation model, we examined how Siglec-7 expression relates to mitochondrial dynamics. Western blotting showed that mitochondrial dynamics-related proteins were markedly altered during PMA-induced differentiation, and confocal imaging revealed that Siglec-7⁺ MK-like cells displayed more elongated, highly branched mitochondrial networks than Siglec-7⁻ one. In parallel, stored human platelets exhibited increased surface Siglec-7 expression. These findings identify Siglec-7 as a candidate regulator linking mitochondrial dynamics to MK differentiation and platelet function.