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巨噬细胞在肾脏发育过程中限制肾源区并促进内皮连接。

Macrophages restrict the nephrogenic field and promote endothelial connections during kidney development.

机构信息

Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh, United Kingdom.

Department of Bioengineering, Bar-Ilan University, Ramat Gan, Israel.

出版信息

Elife. 2019 Feb 13;8:e43271. doi: 10.7554/eLife.43271.

Abstract

The origins and functions of kidney macrophages in the adult have been explored, but their roles during development remain largely unknown. Here we characterise macrophage arrival, localisation, heterogeneity, and functions during kidney organogenesis. Using genetic approaches to ablate macrophages, we identify a role for macrophages in nephron progenitor cell clearance as mouse kidney development begins. Throughout renal organogenesis, most kidney macrophages are perivascular and express F4/80 and CD206. These macrophages are enriched for mRNAs linked to developmental processes, such as blood vessel morphogenesis. Using antibody-mediated macrophage-depletion, we show macrophages support vascular anastomoses in cultured kidney explants. We also characterise a subpopulation of galectin-3 (Gal3) myeloid cells within the developing kidney. Our findings may stimulate research into macrophage-based therapies for renal developmental abnormalities and have implications for the generation of bioengineered kidney tissues.

摘要

肾脏巨噬细胞在成体中的起源和功能已经得到了探索,但它们在发育过程中的作用在很大程度上仍然未知。在这里,我们描述了巨噬细胞在肾脏器官发生过程中的到达、定位、异质性和功能。通过基因敲除的方法去除巨噬细胞,我们发现巨噬细胞在小鼠肾脏发育开始时清除肾祖细胞中发挥作用。在整个肾脏器官发生过程中,大多数肾脏巨噬细胞位于血管周围,并表达 F4/80 和 CD206。这些巨噬细胞富含与发育过程相关的 mRNA,如血管形态发生。通过抗体介导的巨噬细胞耗竭,我们表明巨噬细胞支持培养的肾脏外植体中的血管吻合。我们还在发育中的肾脏中鉴定出了一个半乳糖凝集素-3 (Gal3) 髓样细胞亚群。我们的发现可能会刺激基于巨噬细胞的疗法对肾脏发育异常的研究,并对生物工程肾脏组织的产生具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/706e/6374076/4291edbe6790/elife-43271-fig1.jpg

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