Immune regulation of neuronal stem cells in the medaka retina.

IF 4 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY
Development Pub Date : 2026-09-01 Epub Date: 2026-09-10 DOI:10.1242/dev.205198
Rashi Agarwal, Joergen Benjaminsen, Katharina Lust, Clara Julseth, Natalia Fuchs, Eva Hasel de Carvalho, Fanny Eggeler, Omnia El Said Ibrahim, Narges Aghaallaei, Baubak Bajoghli, Joachim Wittbrodt
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引用次数: 0

Abstract

Stem cell populations in tissues require precise regulation of their number and quality to maintain proper organ growth. Among the various regulatory mechanisms, immune cells are emerging to directly regulate stem cell populations. The medaka retinal stem cell (RSC) niche, a model for lifelong neurogenic growth, provides a system for studying immune-stem cell interactions. We investigate how microglia, which are resident macrophages of the central nervous system, regulate the RSC niche. We identify that bona fide RSCs express the chemokine Ccl25b, while its cognate receptor, Ccr9a, is expressed in microglia. These microglia form a surveillance ring adjacent to the RSC niche and actively phagocytose RSCs. Interference with microglia by deletion of spi1b reveals that microglia absence leads to increased numbers of ccl25b-positive RSCs and results in morphological defects of the retina. Targeted mutation of ccl25b specifically affects microglia mobility under injury conditions; however, we did not observe any morphological defects, indicating that Ccl25b-Ccr9a signaling is not essential for stem cell maintenance. Overall, our data show that, under homeostatic conditions, the individual RSCs, which are essential for proper eye development, are actively phagocytosed by immune surveillance.

medaka视网膜中神经元干细胞的免疫调节。
组织中的干细胞群需要精确调节其数量和质量,以维持适当的器官生长。在多种调节机制中,免疫细胞直接调节干细胞群的机制正在兴起。medaka视网膜干细胞(RSC)生态位是一种终身神经源性生长模型,为研究免疫干细胞相互作用提供了一个系统。我们研究了作为中枢神经系统巨噬细胞的小胶质细胞如何调节RSC生态位。我们发现真正的RSCs表达趋化因子Ccl25b,而其同源受体Ccr9a在小胶质细胞中表达。这些小胶质细胞在RSC生态位附近形成一个监视环,并积极吞噬RSC。spi1b缺失对小胶质细胞的干扰表明,小胶质细胞缺失导致ccl25b阳性RSCs数量增加,并导致视网膜形态缺陷。ccl25b靶向突变特异性影响损伤条件下小胶质细胞的流动性;然而,我们没有观察到任何形态学缺陷,这表明Ccl25b-Ccr9a信号对于干细胞维持不是必需的。总的来说,我们的数据表明,在稳态条件下,对眼睛正常发育至关重要的单个RSCs被免疫监视主动吞噬。
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来源期刊
Development
Development 生物-发育生物学
CiteScore
6.70
自引率
4.30%
发文量
433
审稿时长
3 months
期刊介绍: Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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