C1q is essential for myelination in the central nervous system (CNS)

• Published in: iScience 2023-12, Vol.26 (12), p.108518-108518, Article 108518
• Main Authors: Yu, Qiang, Zhang, Nan, Guan, Teng, Guo, Ying, Marzban, Hassan, Lindsey, Benjamin, Kong, Jiming
• Format: Article
• Language: English
• Subjects: Biological sciences; Developmental neuroscience; Natural sciences; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.108518

Myelin sheath in the central nervous system (CNS) is essential for efficient action potential conduction. Microglia, the macrophages in the CNS, are suggested to regulate myelin development. However, the specific involvement of microglia in initial myelination is yet to be elucidated. Here, first, by culturing neural stem cells, we demonstrated that myelin sheath formation only occurred in the presence of a microglia-conditioned medium. Furthermore, the absence of C1q, a microglia-derived factor, resulted in myelination failure in the neural stem cell culture. Additionally, adding native human C1q protein was sufficient to induce myelination in vitro. Finally, in the C1q conditional knockout mouse model (C1qaFL/FL: Cx3cr1CreER), C1q deficiency prior to the onset of myelination led to reduced myelin thickness and elevated g-ratio during initial myelination. This study uncovers the pivotal role of microglia-derived C1q in developmental myelination and could potentially pave the way for new therapeutic strategies for treating demyelinating diseases. [Display omitted] •Absence of microglia-derived C1q results in myelination failure in vitro•Native human C1q protein is sufficient to induce myelination in vitro•Early C1q deficiency in mouse brains leads to impaired myelin development in vivo Natural sciences; Biological sciences; Neuroscience; Developmental neuroscience