Profound Immune Alterations in the Murine CML Bone Marrow Microenvironment Revealed by Single Cell Ph- Macrophage Profiling and Secretory Proteomics

Macrophages are cells of the innate immune system fundamental to support normal haematopoiesis, fight infection, anti-cancer immunity and tumour progression. However, the function of macrophages in myeloid leukaemias remain largely unknown, due to difficulties in isolating non-transformed cells from the malignant ones. Here we use a state-of-the-art chimeric mouse of chronic myeloid leukaemia (CML) to study in the impact of the dysregulated bone marrow (BM) microenvironment on bystander macrophages. Utilising single cell RNA sequencing (scRNA seq) of Philadelphia chromosome (Ph) negative macrophages and secretome proteomics of murine c-kit+ stem/progenitor cells we have uncovered that macrophages exposed to a CML environment are altered transcriptionally and have reduced phagocytic function

巨噬细胞（Macrophages）是固有免疫系统的核心细胞类群，在维持正常造血功能、抵御病原体感染、介导抗肿瘤免疫以及促进肿瘤进展中均发挥关键作用。然而由于难以从恶性细胞群中分离出非转化型巨噬细胞，髓系白血病中巨噬细胞的功能仍在很大程度上未被阐明。本研究借助前沿的慢性髓系白血病（CML）嵌合小鼠模型，探究失调的骨髓（BM）微环境对旁观者巨噬细胞的影响。本研究通过对费城染色体（Ph）阴性巨噬细胞开展单细胞RNA测序（scRNA seq），并对小鼠c-kit阳性干细胞/祖细胞进行分泌组蛋白质组学分析，发现暴露于CML微环境的巨噬细胞在转录水平发生显著改变，且吞噬功能出现明显下降。