State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.
Dev Cell. 2024 Jan 8;59(1):108-124.e7. doi: 10.1016/j.devcel.2023.11.018. Epub 2023 Dec 14.
Microglia are highly heterogeneous as resident immune cells in the central nervous system. Although the proinflammatory phenotype of microglia is driven by the metabolic transformation in the disease state, the mechanism of metabolic reprogramming in microglia and whether it affects surrounding astrocyte progenitors have not been well elucidated. Here, we illustrate the communication between microglial metabolism and astrogenesis during embryonic development. The transcription factor BTB and CNC homology 1 (Bach1) reduces lactate production by inhibiting two key enzymes, HK2 and GAPDH, during glycolysis. Metabolic perturbation of microglia reduces lactate-dependent histone modification enrichment at the Lrrc15 promoter. The microglia-derived LRRC15 interacts with CD248 to participate in the JAK/STAT pathway and influence astrogenesis. In addition, Bach1 mice exhibit abnormal neuronal differentiation and anxiety-like behaviors. Altogether, this work suggests that the maintenance of microglia metabolic homeostasis during early brain development is closely related to astrogenesis, providing insights into astrogenesis and related diseases.
小胶质细胞作为中枢神经系统中高度异质性的固有免疫细胞。尽管小胶质细胞的促炎表型是由疾病状态下的代谢转化所驱动，但小胶质细胞代谢重编程的机制及其是否影响周围星形细胞前体尚未得到很好的阐明。在这里，我们描述了小胶质细胞代谢和胚胎发育期间星形发生之间的通讯。转录因子 BTB 和 CNC 同源性 1（Bach1）通过抑制糖酵解中的两个关键酶 HK2 和 GAPDH 来减少乳酸的产生。小胶质细胞代谢的扰动会降低 Lrrc15 启动子处依赖于乳酸的组蛋白修饰的富集。小胶质细胞衍生的 LRRC15 与 CD248 相互作用，参与 JAK/STAT 途径，并影响星形发生。此外，Bach1 小鼠表现出异常的神经元分化和焦虑样行为。总的来说，这项工作表明，早期大脑发育中小胶质细胞代谢平衡的维持与星形发生密切相关，为星形发生和相关疾病提供了新的见解。
