Characterization of Cellular Heterogeneity and an Immune Subpopulation of Human Megakaryocytes

Megakaryocytes (MKs) and their progeny platelets function in a variety of biological processes including coagulation, hemostasis, inflammation, angiogenesis, and innate immunity. However, the divergent developmental and cellular landscape of adult MKs remains mysterious. Here, by deriving the single-cell transcriptomic profiling of MKs from human adult bone marrow (BM), cellular heterogeneity within MKs is unveiled and an MK subpopulation with high enrichment of immune-associated genes is identified. By performing the dynamic single-cell transcriptomic landscape of human megakaryopoiesis in vitro, it is found that the immune signatures of MKs can be traced back to the progenitor stage. Furthermore, two surface markers, CD148 and CD48, are identified for mature MKs with immune characteristics. At the functional level, these CD148(+)CD48(+) MKs can respond rapidly to immune stimuli both in vitro and in vivo, exhibit high-level expression of immune receptors and mediators, and may function as immune-surveillance cells. The findings uncover the cellular heterogeneity and a novel immune subset of human adult MKs and should greatly facilitate the understanding of the divergent functions of MKs under physiological and pathological conditions.

Automated summary

The study uncovers cellular heterogeneity in adult MKs, identifies an MK subpopulation with high concentration of immune-related genes, and traces the immune signatures of MKs back to the progenitor stage through in vitro research. Additionally, two surface markers for mature MKs with immune characteristics are identified, allowing for rapid response to immune stimuli and potential immune surveillance functions.