Yolk sac-derived Pdcd11-positive cells modulate zebrafish microglia differentiation through the NF-κB-Tgfβ1 pathway.
Yolk sac-derived Pdcd11-positive cells modulate zebrafish microglia differentiation through the NF-κB-Tgfβ1 pathway.
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DOI：
10.1038/s41418-020-0591-3
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发表时间：
2021-01
影响因子：
12.4
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Yang R;Zhan M;Guo M;Yuan H;Wang Y;Zhang Y;Zhang W;Chen S;de The H;Chen Z;Zhou J;Zhu J
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重要作用。外周造血组织中的小胶质细胞前体在早期胚胎发育期间定殖于中枢神经系统。然而，内源性和外源性信号如何整合来调节小胶质细胞的分化仍不清楚。在这项研究中，我们确定了大脑白色物质高信号易感基因，程序性细胞死亡蛋白11（PDCD 11），作为一个重要的因素调节小胶质细胞分化。在斑马鱼中，pdcd 11缺陷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脑定殖增强。在受精后22小时，卵黄囊上的Pdcd 11阳性细胞不同于巨噬细胞和中性粒细胞。从机制上讲，PDCD 11通过差异调节核因子-κ B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）表达，并增强TGFβ1的c-Rel依赖性表现，发挥其生理作用。本研究为理解斑马鱼发育过程中小胶质细胞的分化提供了新的见解。
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.
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DOI：
10.1136/bmj.c3666
发表时间：
2010-07-26
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Debette S;Markus HS
通讯作者：
Markus HS
影响因子：
3.1
作者：
Harvie, Elizabeth A.;Green, Julie M.;Huttenlocher, Anna
通讯作者：
Huttenlocher, Anna
影响因子：
8.3
作者：
Fornage, Myriam;Chiang, Y. Aron;Longstreth, W. T., Jr.
通讯作者：
Longstreth, W. T., Jr.
影响因子：
4.6
作者：
Hinits, Yaniv;Osborn, Daniel P. S.;Hughes, Simon M.
通讯作者：
Hughes, Simon M.
DOI：
10.1073/pnas.97.21.11403
发表时间：
2000-10-10
影响因子：
11.1
作者：
Kawakami, K;Shima, A;Kawakami, N
通讯作者：
Kawakami, N