Spi1, also known as PU.1, is an E26 transformation-specific sequence-related transcription factor pivotal in hematopoiesis, regulating microglial/macrophage commitment and maturation. It is involved in multiple pathways, such as the PI3K/AKT/mTOR signaling pathway, and plays a significant role in various biological processes and disease conditions [1].

In Alzheimer's disease (AD) mouse models, Spi1 knockdown exacerbates amyloid-β aggregation, amyloid plaque deposition, and gliosis, while overexpression ameliorates these phenotypes. This indicates that Spi1-mediated transcriptome remodeling impacts AD-related phenotypes, potentially modulating immune response and complement system pathways [3]. In intracerebral hemorrhage, Spi1 may regulate recovery from neuroinflammation and neurofunctional damage by modulating the microglial/macrophage transcriptome [1]. In age-related macular degeneration, Spi1-mediated macrophage polarization aggravates the disease, and its suppression inhibits M1 polarization and attenuates neovascularization [2].

In conclusion, Spi1 is a crucial transcription factor in myeloid cell development and immune-related processes. Studies using gene knockout or overexpression mouse models have revealed its significant role in diseases like AD, intracerebral hemorrhage, and age-related macular degeneration. These findings provide potential therapeutic targets for these diseases by understanding the function of Spi1 in relevant biological processes.

References:

1. Zhang, Guoqiang, Lu, Jianan, Zheng, Jingwei, Fang, Yuanjian, Yu, Jun. . Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage. In Neural regeneration research, 19, 161-170. doi:10.4103/1673-5374.375343. https://pubmed.ncbi.nlm.nih.gov/37488863/

2. Qi, Siyi, Zhang, Yihan, Kong, Lingjie, Zhang, Shujie, Zhao, Chen. 2024. SPI1-mediated macrophage polarization aggravates age-related macular degeneration. In Frontiers in immunology, 15, 1421012. doi:10.3389/fimmu.2024.1421012. https://pubmed.ncbi.nlm.nih.gov/38979414/

3. Kim, Byungwook, Dabin, Luke Child, Tate, Mason Douglas, Jucker, Mathias, Kim, Jungsu. 2024. Effects of SPI1-mediated transcriptome remodeling on Alzheimer's disease-related phenotypes in mouse models of Aβ amyloidosis. In Nature communications, 15, 3996. doi:10.1038/s41467-024-48484-x. https://pubmed.ncbi.nlm.nih.gov/38734693/