Liver macrophages in YapS127A and wildtype livers

Disturbance of heterologous cell communication is associated with a structural reorganization of the vascular niche, a process called capillarization, which is already initiated in early stages of liver tumor development. In this study, the molecular characterization of endothelial cell (EC) subpopulations from healthy livers and yes-associated protein (Yap)-induced liver tumors revealed a dynamic crosstalk between liver sinusoidal endothelial cells (LSECs) and capillary endothelial cells (CECs). Initial paracrine stimuli from parenchymal cells include the Yap/Tead4 target gene osteopontin (Opn), which promotes CECs expansion through the induction of c-Met and sensitization towards LSEC-derived hepatocyte growth factor (Hgf). In addition, Yap/Tead4-induced C-C motif chemokine ligand 2 (Ccl2) recruits bone-marrow-derived macrophages (BMDMs) with an unpolarized phenotype (M0) to the perivascular space of expanding CECs. 8 samples: 4 macrophage samples derived from wildtype livers and 4 macrophage samples derived from YapS127A tumor bearing livers.

异源细胞通讯紊乱与血管微环境（vascular niche）的结构重编程密切相关，这一过程被称为毛细血管化（capillarization），且在肝肿瘤发生的早期阶段即已启动。本研究对健康肝脏以及由Yes相关蛋白（yes-associated protein, Yap）诱导形成的肝肿瘤中的内皮细胞（endothelial cell, EC）亚群进行了分子表征，揭示了肝窦内皮细胞（liver sinusoidal endothelial cells, LSECs）与毛细血管内皮细胞（capillary endothelial cells, CECs）之间存在动态串扰。实质细胞初始分泌的旁分泌刺激因子包括Yap/Tead4靶基因骨桥蛋白（osteopontin, Opn），其可通过诱导c-Met表达并增强对肝窦内皮细胞来源的肝细胞生长因子（hepatocyte growth factor, Hgf）的敏感性，从而促进毛细血管内皮细胞的增殖扩张。此外，Yap/Tead4诱导产生的C-C基序趋化因子配体2（C-C motif chemokine ligand 2, Ccl2）可将具有未极化表型（M0）的骨髓来源巨噬细胞（bone-marrow-derived macrophages, BMDMs）招募至正在扩张的毛细血管内皮细胞的血管周间隙。本数据集共包含8份样本：4份取自野生型肝脏的巨噬细胞样本，以及4份取自携带YapS127A突变肿瘤的肝脏的巨噬细胞样本。