Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes
Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes
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DOI：
10.7554/elife.53403
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发表时间：
2020-05-05
期刊：
影响因子：
7.7
通讯作者：
van Ham, Tjakko J.
中科院分区：
文献类型：
--
作者：
Kuil, Laura E.;Oosterhof, Nynke;van Ham, Tjakko J.
巨噬细胞来源于造血祖细胞的多种来源。大多数巨噬细胞需要集落刺激因子 1 受体 (CSF1R)，但有些巨噬细胞在缺乏 CSF1R 的情况下仍存在。在这里，我们分析了 csf1r 缺陷斑马鱼中表达 mpeg1:GFP 的巨噬细胞，并报告胚胎巨噬细胞出现后发育停滞。在幼虫中，mpeg1+细胞数量随后增加，在皮肤中显示出两种不同的类型：分支的、假定的朗格汉斯细胞和变形虫细胞。相比之下，尽管 csf1r 突变体的数量也有所增加，但仅存在变形虫 mpeg1+ 细胞，我们通过遗传谱系追踪表明其具有非造血起源。它们表达巨噬细胞相关基因，但也表现出吞噬细胞基因表达减少和上皮相关基因表达增加，这是最近发现的外胚层衍生细胞的特征。我们进一步证明，csf1r 缺陷的幼年斑马鱼表现出系统性巨噬细胞耗竭。因此，csf1r 缺陷会破坏胚胎到成人巨噬细胞的发育。缺乏 csf1r 的斑马鱼是可行的，并允许分析一生中巨噬细胞损失的后果。
Macrophages derive from multiple sources of hematopoietic progenitors. Most macrophages require colony-stimulating factor 1 receptor (CSF1R), but some macrophages persist in the absence of CSF1R. Here, we analyzed mpeg1:GFP-expressing macrophages in csf1r-deficient zebrafish and report that embryonic macrophages emerge followed by their developmental arrest. In larvae, mpeg1+ cell numbers then increased showing two distinct types in the skin: branched, putative Langerhans cells, and amoeboid cells. In contrast, although numbers also increased in csf1r-mutants, exclusively amoeboid mpeg1+ cells were present, which we showed by genetic lineage tracing to have a non-hematopoietic origin. They expressed macrophage-associated genes, but also showed decreased phagocytic gene expression and increased epithelial-associated gene expression, characteristic of metaphocytes, recently discovered ectoderm-derived cells. We further demonstrated that juvenile csf1r-deficient zebrafish exhibit systemic macrophage depletion. Thus, csf1r deficiency disrupts embryonic to adult macrophage development. Zebrafish deficient for csf1r are viable and permit analyzing the consequences of macrophage loss throughout life.