淋巴系统
颅缝病
颅骨
脑膜
生物
祖细胞
解剖
病理
血管生成
神经科学
医学
细胞生物学
免疫学
癌症研究
干细胞
作者
Li Ma,Qing Chang,Fei Pei,Mengmeng Liu,Wei Zhang,Young‐Kwon Hong,Yang Chai,Jian-Fu Chen
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2023-11-01
卷期号:30 (11): 1472-1485.e7
被引量:4
标识
DOI:10.1016/j.stem.2023.09.012
摘要
The meninges lie in the interface between the skull and brain, harboring lymphatic vasculature and skull progenitor cells (SPCs). How the skull and brain communicate remains largely unknown. We found that impaired meningeal lymphatics and brain perfusion drive neurocognitive defects in Twist1+/- mice, an animal model of craniosynostosis recapitulating human Saethre-Chotzen syndrome. Loss of SPCs leads to skull deformities and elevated intracranial pressure (ICP), whereas transplanting SPCs back into mutant mice mitigates lymphatic and brain defects through two mechanisms: (1) decreasing elevated ICP by skull correction and (2) promoting the growth and migration of lymphatic endothelial cells (LECs) via SPC-secreted vascular endothelial growth factor-C (VEGF-C). Treating Twist1+/- mice with VEGF-C promotes meningeal lymphatic growth and rescues defects in ICP, brain perfusion, and neurocognitive functions. Thus, the skull functionally integrates with the brain via meningeal lymphatics, which is impaired in craniosynostosis and can be restored by SPC-driven lymphatic activation via VEGF-C.
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