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Yolk sac-derived Pdcd11-positive cells modulate zebrafish microglia differentiation through the NF-κB-Tgfβ1 pathway.
Cell Death and Differentiation ( IF 12.4 ) Pub Date : 2020-07-24 , DOI: 10.1038/s41418-020-0591-3
Ruimeng Yang 1, 2 , Ming Zhan 2, 3 , Miaomiao Guo 2 , Hao Yuan 1 , Yiqin Wang 1 , Yiyue Zhang 4 , Wenqing Zhang 4 , Saijuan Chen 1 , Hugues de The 1, 5, 6 , Zhu Chen 1 , Jun Zhou 1 , Jun Zhu 1, 5
Affiliation  

Microglia are the primary immune cells in the central nervous system, which plays a vital role in neuron development and neurodegenerative diseases. Microglial precursors in peripheral hematopoietic tissues colonize the central nervous system during early embryogenesis. However, how intrinsic and extrinsic signals integrate to regulate microglia’s differentiation remains undefined. In this study, we identified the cerebral white matter hyperintensities susceptibility gene, programmed cell death protein 11 (PDCD11), as an essential factor regulating microglia differentiation. In zebrafish, pdcd11 deficiency prevents the differentiation of the precursors to mature brain microglia. Although, the inflammatory featured macrophage brain colonization is augmented. At 22 h post fertilization, the Pdcd11-positive cells on the yolk sac are distinct from macrophages and neutrophils. Mechanistically, PDCD11 exerts its physiological role by differentially regulating the functions of nuclear factor-kappa B family members, P65 and c-Rel, suppressing P65-mediated expression of inflammatory cytokines, such as tnfα, and enhancing the c-Rel-dependent appearance of tgfβ1. The present study provides novel insights in understanding microglia differentiation during zebrafish development.



中文翻译:

卵黄囊衍生的 Pdcd11 阳性细胞通过 NF-κB-Tgfβ1 通路调节斑马鱼小胶质细胞分化。

小胶质细胞是中枢神经系统的主要免疫细胞,在神经元发育和神经退行性疾病中起着至关重要的作用。外周造血组织中的小胶质细胞前体在早期胚胎发生过程中定植于中枢神经系统。然而,内在和外在信号如何整合以调节小胶质细胞的分化仍未确定。在这项研究中,我们确定了大脑白质高信号易感基因,程序性细胞死亡蛋白 11 ( PDCD11 ),作为调节小胶质细胞分化的重要因素。在斑马鱼中,pdcd11缺乏会阻止前体分化为成熟的脑小胶质细胞。尽管如此,炎症特征的巨噬细胞大脑定植增加了。受精后 22 小时,卵黄囊上的 Pdcd11 阳性细胞与巨噬细胞和中性粒细胞不同。从机制上讲,PDCD11 通过差异调节核因子-κB 家族成员 P65 和 c-Rel 的功能,抑制 P65 介导的炎性细胞因子(如tnfα)的表达,并增强 c-Rel 依赖的外观来发挥其生理作用。 tgfβ1。本研究为了解斑马鱼发育过程中的小胶质细胞分化提供了新的见解。

更新日期:2020-07-24
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