Pu.1/Spi1剂量控制斑马鱼和哺乳动物小胶质细胞的周转和维持。

IF 6.4 1区 生物学 Q1 BIOLOGY
eLife Pub Date : 2025-07-17 DOI:10.7554/eLife.105788
Yi Wu, Weilin Guo, Haoyue Kuang, Xiaohai Wu, Thi Huong Trinh, Yuexin Wang, Shizheng Zhao, Zilong Wen, Tao Yu
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引用次数: 0

摘要

小胶质细胞是脑内巨噬细胞,在中枢神经系统(CNS)的发育和稳态中起着关键作用。然而,控制小胶质细胞维持的细胞和分子基础在很大程度上仍然未知。在这里,利用一个可见的条件敲除等位基因pu。1/spi1b基因(小胶质细胞/巨噬细胞谱系发育的主要调控因子)在成年斑马鱼中产生马赛克小胶质细胞群体。缺乏1的小胶质细胞可以立即存活,它们的竞争能力较弱,并通过tp53介导的细胞竞争被慢性消除。有趣的是,当在成年spi-b(小鼠spi-b的同源物)零突变体中条件失活Pu.1时,小胶质细胞通过凋亡迅速耗尽,这表明Pu.1和spi-b以剂量依赖的方式调节小胶质细胞的维持。PU.1/SPI1对小胶质细胞维持的剂量依赖性调控在小鼠中具有进化保守性,分别在小胶质细胞中条件失活单个和两个SPI1等位基因。总的来说,我们的研究揭示了在硬骨鱼和哺乳动物中控制小胶质细胞转换和维持的保守的细胞和分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals.

Microglia are brain-resident macrophages playing pivotal roles in central nervous system (CNS) development and homeostasis. Yet, the cellular and molecular basis governing microglia maintenance remains largely unknown. Here, by utilizing a visible conditional knockout allele of pu.1/spi1b gene (the master regulator for microglia/macrophage lineage development) to generate mosaic microglia populations in adult zebrafish, we show that while pu.1-deficient microglia are immediately viable, they are less competitive, and chronically eliminated through Tp53-mediated cell competition. Interestingly, when conditionally inactivating Pu.1 in adult spi-b (the orthologue of mouse Spi-b) null mutants, microglia are rapidly depleted via apoptosis, suggesting that Pu.1 and Spi-b regulate microglia maintenance in a dosage-dependent manner. The dosage-dependent regulation of microglia maintenance by PU.1/SPI1 is evolutionarily conserved in mice, as shown by conditionally inactivating single and both Spi1 alleles in microglia, respectively. Collectively, our study reveals the conserved cellular and molecular mechanisms controlling microglia turnover and maintenance in teleosts and mammals.

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来源期刊
eLife
eLife BIOLOGY-
CiteScore
12.90
自引率
3.90%
发文量
3122
审稿时长
17 weeks
期刊介绍: eLife is a distinguished, not-for-profit, peer-reviewed open access scientific journal that specializes in the fields of biomedical and life sciences. eLife is known for its selective publication process, which includes a variety of article types such as: Research Articles: Detailed reports of original research findings. Short Reports: Concise presentations of significant findings that do not warrant a full-length research article. Tools and Resources: Descriptions of new tools, technologies, or resources that facilitate scientific research. Research Advances: Brief reports on significant scientific advancements that have immediate implications for the field. Scientific Correspondence: Short communications that comment on or provide additional information related to published articles. Review Articles: Comprehensive overviews of a specific topic or field within the life sciences.
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