Journal article

Brief Report: Factors Released by Megakaryocytes Thrombin Cleave Osteopontin to Negatively Regulate Hematopoietic Stem Cells

Melonie J Storan, Shen Y Heazlewood, Chad K Heazlewood, David N Haylock, Warren S Alexander, Rebecca J Neaves, Ana Oteiza, Susan K Nilsson

STEM CELLS | WILEY | Published : 2015


Factor V (FV) and factor X (FX) activate and complex to form prothrombinase which subsequently cleaves prothrombin (PT), converting it to active thrombin. Thrombin cleaved osteopontin (tcOPN) contains a cryptic binding site for α4 β1 and α9 β1 integrins. We have previously shown that hematopoietic stem cells (HSC) bind to tcOPN via this site resulting in a decrease in their proliferation and differentiation. Therefore, tcOPN and the factors required for its generation are important components of the HSC niche. Herein we show mature megakaryocytes (MM, ≥8N) contain FV, FX, and PT mRNA and protein. Furthermore, we show 8N, 16N, 32N, and 64N MM all release the required factors to enable thrombi..

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Funding Acknowledgements

The authors thank Brenda Williams and Andrea Reitsma for assistance with cell processing, Daniela Cardozo, and Jessica Hatwell-Humble for assistance with animal work, Esben Sorensen for the provision of human breast milk OPN and members of FlowCore (Monash University, Australia) for flow cytometric support. A CSIRO OCE Science Leaders Fellowship to S.K.N. and a SIEF grant to S.K.N, D.N.H., and W.S.A. in part funded this work. W.S.A. was supported by a program grant, a fellowship, and an IRIISS grant from the NHMRC, the ACRF and Victorian State Government Operational Infrastructure Support.