C1q is essential for myelination in the central nervous system (CNS)
Qiang Yu,
Nan Zhang,
Teng Guan,
Ying Guo,
Hassan Marzban,
Benjamin Lindsey,
Jiming Kong
Affiliations
Qiang Yu
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada
Nan Zhang
The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Hebei Hospital Xuanwu Hospital of Capital Medical University, Neuromedical Technology Innovation Center of Hebei Province, Shijiazhuang, Hebei, China
Teng Guan
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada
Ying Guo
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada; Department of Forensic Medicine, Hebei North University, Zhangjiakou, Hebei, China
Hassan Marzban
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada
Benjamin Lindsey
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada
Jiming Kong
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada; Corresponding author
Summary: 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.
