Abstract Number: PB1609
Meeting: ISTH 2020 Congress
Background: Megakaryocytes (MKs) come from a complex hematopoietic progenitor maturation process within the bone marrow (BM) that give rise to de novo circulating platelets. BM microenvironment contains a large number of adipocytes which medullar role remains ill-defined. It has been shown that either bone marrow adipocytes in a steady state or under high-fat-diet -induced obesity that increases medullar adiposity content have an impact on general hematopoiesis, lymphopoiesis and myelopoiesis. This make the adipocyte an influent member of the BM niche whereas for a long time adipocytes have been considered as passive BM “space fillers”.
Aims: Considering the critical influence of BM niche for a normal hematopoiesis and the susceptibility of BM microenvironment to obesity, we addressed the question whether adipocytes and increased medullar adiposity could influence medullar megakaryopoiesis.
Methods: To that aim, increased medullar adiposity linked to obesity was induced in mouse by a 12 weeks high-fat-diet. In parallel, we set up an in vitro co-culture assay where freshly isolated hematopoietic progenitors from mouse BM directed towards megakaryocytic maturation by thrombopoietin were co-cultivated with adipocytes without any direct contact.
Results: We showed for the first time that an increased medullar adiposity in vivo caused by high-fat-diet was associated to an enhanced MK nuclear and membrane maturation along with a faster proplatelet formation. In vitro co-culture experiments allowed to demonstrate that, in one hand, adipocytes directly support MK maturation by enhancing polyploidization, amplifying demarcation membrane system and accelerating proplatelet formation and that, in another hand, MKs are responsible for adipocyte delipidation and dedifferentiation. Interestingly, we further showed the existence of an unsuspected crosstalk between adipocytes and MKs through a direct adipocyte fatty acid transfer dedicated to hematopoietic progenitors to reinforce MK maturation.
Conclusions: Thus, these findings unveiled a hitherto unrecognized influence of adiposity on MK homeostasis based on a dialogue between adipocytes and MKs.
To cite this abstract in AMA style:Valet C, Batut A, Vauclard A, Dortignac A, Bellio M, Payrastre B, Valet P, Severin S. A Close Relationship between Adipocytes and Megakaryocytes [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/a-close-relationship-between-adipocytes-and-megakaryocytes/. Accessed March 4, 2024.
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