彼得麦卡勒姆癌症中心Benjamin M. Hogan小组在研究中取得进展。他们提出了脑边界清道夫细胞发育的趋同进化。2026年1月21日出版的《自然》发表了这项成果。

在这里，课题组人员发现转录因子odd-skipped related （osr2）是muLEC分化和维持的特定标记和调节因子。osr2部分通过控制钙粘蛋白-6来控制muLECs从相互连接的内皮细胞向单个清除细胞的转变。与其他哺乳动物脑膜细胞相比，muLECs在转录上与BAMs更相似，并且在组织稳态中具有几种相同的功能。

然而，斑马鱼和小鼠和人类的muLECs中不存在BAMs。对不同脊椎动物物种的osr2、淋巴内皮细胞（LEC）和BAM标记物的分析表明，muLECs是一个古老的谱系，而BAM是最近的哺乳动物特化。muLECs和BAMs在功能上有相似之处，但不是同源的，这是趋同进化的一个例子。这突出了脑膜清道夫细胞的生理重要性和脑膜清道夫细胞在进化过程中产生特化细胞类型的发育可塑性。

据了解，脊椎动物的中枢神经系统受到血脑屏障和脑膜的保护，这确保了免疫特权。在哺乳动物大脑中，小胶质细胞和屏障相关或边界相关巨噬细胞（BAMs）提供免疫监视和清除废物，但进化如何塑造免疫细胞的多样性和功能尚不清楚。在斑马鱼中，血管来源的壁淋巴内皮细胞（muLEC）谱系在中枢神经系统边界履行清道夫细胞功能。

附：英文原文

Title: Convergent evolution of scavenger cell development at brain borders

Author: Gaudi, Andrea U., Meier, Michelle, Baltaci, Oguzhan F., Chowdhary, Sayali, Tulenko, Frank J., Dudczig, Stefanie, Stamatis, Sebastian-Alexander, Paterson, Scott, Yu, Hujun, Galeano, Maria Cristina Rondon, Mason, Elizabeth, Miles, Lee B., Bryson-Richardson, Robert J., Pask, Andrew J., Vukovic, Jana, Lagendijk, Anne K., Smith, Kelly A., Kaslin, Jan, Harrison, Michael RM, Currie, Peter D., Bower, Neil I., Hogan, Benjamin M.

Issue&Volume: 2026-01-21

Abstract: The vertebrate central nervous system is protected by the blood–brain barrier and meningeal membranes, which ensure immune privilege1. In the mammalian brain, microglia and barrier-associated or border-associated macrophages (BAMs) provide immune surveillance and scavenge wastes2, yet how evolution shaped immune-cell diversity and function is not understood. In zebrafish, a vascular-derived mural lymphatic endothelial cell (muLEC) lineage fulfils scavenger cell functions at central nervous system borders3,4,5. Here we identify the transcription factor odd-skipped related 2 (osr2) as a specific marker and regulator of muLEC differentiation and maintenance. osr2 controls the transition of muLECs from interconnected endothelial cells to individual scavenger cells in part by means of control of cadherin-6. muLECs are more transcriptionally similar to BAMs than to other mammalian meningeal cells and share several functions in tissue homeostasis. However, BAMs are absent from zebrafish and muLECs from mice and humans. Analysis of osr2, lymphatic endothelial cell (LEC) and BAM markers in diverse vertebrate species reveals muLECs as an ancient lineage and BAMs a recent mammalian specialization. muLECs and BAMs share functional analogies but are not homologous, providing an example of convergent evolution. This highlights the physiological importance of meningeal scavenger cells and the developmental plasticity of LECs in generating specialized cell types throughout evolution.

DOI: 10.1038/s41586-025-10003-3

Source: https://www.nature.com/articles/s41586-025-10003-3