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..View full abstract
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.