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Skull progenitor cell-driven meningeal lymphatic restoration improves neurocognitive functions in craniosynostosis.

Authors :
Ma L
Chang Q
Pei F
Liu M
Zhang W
Hong YK
Chai Y
Chen JF
Source :
Cell stem cell [Cell Stem Cell] 2023 Nov 02; Vol. 30 (11), pp. 1472-1485.e7. Date of Electronic Publication: 2023 Oct 19.
Publication Year :
2023

Abstract

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 <superscript>+/-</superscript> 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 <superscript>+/-</superscript> 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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1875-9777
Volume :
30
Issue :
11
Database :
MEDLINE
Journal :
Cell stem cell
Publication Type :
Academic Journal
Accession number :
37863055
Full Text :
https://doi.org/10.1016/j.stem.2023.09.012