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时空分辨率命运图谱揭示斑马鱼胚胎和成年小胶质细胞的不同起源。

Temporal-Spatial Resolution Fate Mapping Reveals Distinct Origins for Embryonic and Adult Microglia in Zebrafish.

机构信息

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, PRC.

Department of Electronic and Computer Engineering, Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, PRC.

出版信息

Dev Cell. 2015 Sep 28;34(6):632-41. doi: 10.1016/j.devcel.2015.08.018.

Abstract

Microglia are CNS resident macrophages, and they play important roles in neural development and function. Recent studies have suggested that murine microglia arise from a single source, the yolk sac (YS), yet these studies lack spatial resolution to define the bona fide source(s) for microglia. Here, using light-induced high temporal-spatial resolution fate mapping, we challenge this single-source view by showing that microglia in zebrafish arise from multiple sources. The embryonic/larval microglia originate from the rostral blood island (RBI) region, the equivalent of mouse YS for myelopoiesis, whereas the adult microglia arise from the ventral wall of dorsal aorta (VDA) region, a tissue also producing definitive hematopoiesis in mouse. We further show that the VDA-region-derived microglia are Runx1 dependent, but cMyb independent, and developmentally regulated differently from the RBI region-derived microglia. Our study establishes a new paradigm for investigating the development and function of distinct microglia populations.

摘要

小胶质细胞是中枢神经系统常驻巨噬细胞,它们在神经发育和功能中发挥重要作用。最近的研究表明,鼠类小胶质细胞起源于一个单一的来源,即卵黄囊(YS),但这些研究缺乏空间分辨率来确定小胶质细胞的真实来源。在这里,我们使用光诱导的高时空分辨率示踪方法,通过显示斑马鱼中的小胶质细胞起源于多个来源,对这种单一来源的观点提出了挑战。胚胎/幼虫小胶质细胞起源于颅前血岛(RBI)区域,相当于小鼠的 YS 用于髓样细胞生成,而成年小胶质细胞起源于背主动脉(VDA)区域的腹侧壁,该组织在小鼠中也产生定型造血。我们进一步表明,VDA 区域衍生的小胶质细胞依赖于 Runx1,但不依赖于 cMyb,并且与 RBI 区域衍生的小胶质细胞在发育上受到不同的调节。我们的研究为研究不同小胶质细胞群体的发育和功能建立了一个新的范例。

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