Department of Neuropathology, University of Freiburg, Freiburg, Germany.
Nat Neurosci. 2013 Mar;16(3):273-80. doi: 10.1038/nn.3318. Epub 2013 Jan 20.
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.
小胶质细胞对于大脑中的免疫反应至关重要。尽管它们源自卵黄囊的起源已经被认识了一段时间，但它们的确切前体和使用的转录程序尚不清楚。我们发现，小鼠小胶质细胞源自原始的 c-kit(+)红髓前体细胞，这些前体细胞早在受精后 8 天就可以在卵黄囊中检测到。这些前体细胞发育成 CD45(+) c-kit(lo) CX(3)CR1(-)未成熟（A1）细胞，并成熟为 CD45(+) c-kit(-) CX(3)CR1(+) (A2)细胞，这一点可以从 CD31 的下调和 F4/80 和巨噬细胞集落刺激因子受体（MCSF-R）的同时上调得到证明。增殖的 A2 细胞成为小胶质细胞，并使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 Pu.1（也称为 Sfpi），还需要 Irf8，这对于 A2 群体的发育至关重要，而 Myb、Id2、Batf3 和 Klf4 则不需要。我们的数据为小胶质细胞的起源和发育提供了细胞和分子方面的见解。
