RNA-seq analysis of Jak2-V617F monocytes in elastic versus viscous fibrotic matrix

Myelofibrosis (MF) is a progressive, bone marrow (BM) malignancy associated with monocytosis, and is believed to promote the pathological remodelling of the extracellular matrix. Here, we show that the mechanical properties of MF, namely the liquid-to-solid properties (viscoelasticity) of BM, contribute to aberrant differentiation of monocytes. Human monocytes cultured in stiff, elastic hydrogels show pro-inflammatory polarization and differentiation towards dendritic cells, as opposed to those cultured in a viscoelastic matrix. Overall design: Bone marrow-derived monocytes were isolated from control mice (Vav-iCre) and a knock-in murine model of MPN harboring an endogenous Jak2-V617F49 mutation (Jak2-V617F-Vav-iCre). Similar to studies with human cells, monocytes were encapsulated in viscous, stiff and elastic, stiff artificial ECM to determine the impact of elasticity.