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. 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.

骨髓纤维化（Myelofibrosis, MF）是一类伴随单核细胞增多症的进展性骨髓（bone marrow, BM）恶性肿瘤，被认为可促进细胞外基质（extracellular matrix, ECM）的病理性重塑。本研究证实，MF的力学特性——即骨髓的液-固转化特性（粘弹性）——可诱导单核细胞发生异常分化。在刚性弹性水凝胶中培养的人单核细胞，会呈现促炎极化表型并向树突状细胞分化，这与在粘弹性基质中培养的单核细胞表现截然不同。研究人员从对照小鼠（Vav-iCre）以及携带内源性Jak2-V617F49突变的骨髓增殖性肿瘤（MPN）敲入小鼠模型（Jak2-V617F-Vav-iCre）中分离得到骨髓源性单核细胞。与人体细胞实验结果一致，研究人员将单核细胞包埋于粘性、刚性及弹性的人工细胞外基质中，以探究基质弹性的影响。

搜集汇总

背景与挑战

背景概述

该数据集通过RNA测序分析Jak2-V617F突变小鼠单核细胞在弹性与粘性纤维化基质中的基因表达变化，研究骨髓纤维化微环境中基质机械性质对单核细胞分化的调控作用。实验设计使用对照和突变小鼠模型，在人工细胞外基质中模拟不同机械环境，旨在揭示力学检查点在病理重塑中的关键机制。