Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways
Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways
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DOI：
10.1038/nn.3318
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发表时间：
2013-03-01
影响因子：
25
通讯作者：
Prinz, Marco
中科院分区：
文献类型：
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作者：
Kierdorf, Katrin;Erny, Daniel;Prinz, Marco
小胶质细胞对大脑的免疫反应至关重要。虽然人们已经认识到它们起源于卵黄囊已经有一段时间了，但它们的确切前体和使用的转录程序尚不清楚。我们发现小鼠小胶质细胞来源于原始的c-kit(+)红系前体，早在妊娠8d后就在卵黄囊中检测到。这些前体细胞发育成CD45(+)c-kit(Lo)Cx(3)CR1(-)未成熟(A1)细胞，成熟为CD45(+)c-kit(-)Cx(3)CR1(+)(A2)细胞，CD31表达下调，F4/80和巨噬细胞集落刺激因子受体(MCSF-R)表达上调。增殖的A2细胞变成小胶质细胞，并利用特定的基质金属蛋白酶侵入发育中的大脑。值得注意的是，小胶质细胞的发生不仅依赖于转录因子PU1(也称为SFPI)，而且还需要IRF8，这对A2群体的发育至关重要，而Myb、Id2、BATF3和KLF4则不是必需的。我们的数据为小胶质细胞的起源和发展提供了细胞和分子方面的见解。
Microglia are crucial for immune responses in the brain. Although their origin from the yolk sac has been recognized for some time, their precise precursors and the transcription program that is used are not known. We found that mouse microglia were derived from primitive c-kit(+) erythromyeloid precursors that were detected in the yolk sac as early as 8 d post conception. These precursors developed into CD45(+) c-kit(lo) CX(3)CR1(-) immature (A1) cells and matured into CD45(+) c-kit(-) CX(3)CR1(+) (A2) cells, as evidenced by the downregulation of CD31 and concomitant upregulation of F4/80 and macrophage colony stimulating factor receptor (MCSF-R). Proliferating A2 cells became microglia and invaded the developing brain using specific matrix metalloproteinases. Notably, microgliogenesis was not only dependent on the transcription factor Pu.1 (also known as Sfpi), but also required Irf8, which was vital for the development of the A2 population, whereas Myb, Id2, Batf3 and Klf4 were not required. Our data provide cellular and molecular insights into the origin and development of microglia.