中文摘要：

损伤后的无菌炎症对于组织恢复很重要。在受伤的人和小鼠组织中，最近发现巨噬细胞在血管周围积累。本研究调查巨噬细胞是否采用对缺血性损伤后恢复很重要的壁细胞表型。来自缺血性小鼠肌肉的命运定位巨噬细胞的单细胞 RNA 测序显示，具有下调髓系细胞基因和上调壁细胞基因（包括 PDGFRβ）的巨噬细胞亚群存在巨噬细胞向壁细胞的转换。当在分析中包括未拼接的转录本时，这一观察结果得到了进一步加强。巨噬细胞转换被证明具有功能相关性，因为巨噬细胞特异性 PDGFRβ 缺乏症的诱导阻止了其血管周围巨噬细胞表型、受损血管成熟和增加血管渗漏，最终降低了肢体功能。总之，成体缺血组织中的巨噬细胞被证明经历了细胞程序，在形态学、转录组和功能上类似于壁细胞，同时削弱了它们的巨噬细胞特性。巨噬细胞到壁细胞样表型转换对于恢复组织功能至关重要，值得进一步探索作为免疫疗法促进愈合的潜在靶点。

英文摘要：

Sterile inflammation after injury is important for tissue restoration. In injured human and mouse tissues, macrophages were recently found to accumulate perivascularly. This study investigates if macrophages adopt a mural cell phenotype important for restoration after ischemic injury. Single-cell RNA sequencing of fate-mapped macrophages from ischemic mouse muscles demonstrates a macrophage-toward-mural cell switch of a subpopulation of macrophages with downregulated myeloid cell genes and upregulated mural cell genes, including PDGFRβ. This observation was further strengthened when including unspliced transcripts in the analysis. The macrophage switch was proven functionally relevant, as induction of macrophage-specific PDGFRβ deficiency prevented their perivascular macrophage phenotype, impaired vessel maturation and increased vessel leakiness, which ultimately reduced limb function. In conclusion, macrophages in adult ischemic tissue were demonstrated to undergo a cellular program to morphologically, transcriptomically and functionally resemble mural cells while weakening their macrophage identity. The macrophage-to-mural cell-like phenotypic switch is crucial for restoring tissue function and warrants further exploration as a potential target for immunotherapies to enhance healing.

论文信息：

论文题目：Macrophages upregulate mural cell-like markers and support healing of ischemic injury by adopting functions important for vascular support

期刊名称：Nature Cardiovascular Research

时间期卷：3, 685–700 (2024)pages685–700 (2024)

在线时间：2024年6月6日

清除给药策略：

为了确定巨噬细胞是否有助于壁细胞覆盖，我们在胰岛移植前后给予氯膦酸盐脂质体Clodronateliposomes以清除巨噬细胞。与移植到接受对照脂质体（Control Liposomes）的小鼠的胰岛相比，氯膦酸盐脂质体（Clodronate Liposomes）处理导致移植胰岛中巨噬细胞被耗竭92.8±0.1%（图5e）

参考意义：

我们在用荷兰liposoma品牌Clodronateliposomes清除巨噬细胞时，评价自己的清除体系，可以参照该文献的圈门策略。时刻记住，巨噬细胞的异质性，以及在模型发生和发展过程中的动态变化。参考文献时，即使一样的模型，由于采样时间点不同，巨噬细胞的清除，也有可能不太一致。

材料方法：