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. 2020 Mar 12;10:4621. doi: 10.1038/s41598-020-61309-3

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Megakaryocytes contain extranuclear histones, which are passed on to platelets. The proposed mechanism for the development of platelet-associated histones (PAHs). A mononuclear hematopoietic stem cell (HSC) differentiates into a megakaryoblast and undergoes endomitoses to form multiple nuclei. The nuclei (purple) contain various intranuclear histones (green circles). Once differentiation is complete and a mature megakaryocyte is made, the cell begins undergoing a controlled apoptosis, where the nuclear membrane develops pores and histones begin to leak into the cytoplasmic compartment. Upon the formation of proplatelet buds, the cytoplasmic and cell membrane-associated histones are also packed into the resultant platelets. The histones can be present in histones either primarily bound to the cell membrane (1), primarily within the cytoplasm (2), or a combination of the 1 and 2, where platelet activation results in the increased expression of histones on the cell membrane and possible release into the environment accompanied by degranulation.