Distinct molecular profiles of skull bone marrow in health and neurological disorders.

The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature. 3D imaging demonstrates the structural and cellular details of human skull-meninges connections (SMCs) compared with veins. Last, using translocator protein positron emission tomography (TSPO-PET) imaging, we show that the skull bone marrow reflects inflammatory brain responses with a disease-specific spatial distribution in patients with various neurological disorders. The unique molecular profile and anatomical and functional connections of the skull show its potential as a site for diagnosing, monitoring, and treating brain diseases. [Display omitted] • Bone marrow across the body display molecular heterogeneity in mice and humans • Calvaria cells have a distinct profile that is relevant to brain pathologies • Structural details of human skull-meninges connections are revealed • TSPO-PET imaging of human skulls can be a proxy of neuroinflammation in the brain The bone marrow of the skull has a unique molecular and functional composition, as well as disease-specific inflammatory responses that can be observed through human translocator protein positron emission tomography (TSPO-PET) imaging, suggesting that it has potential as a site for brain disease diagnosis, monitoring, and treatment. [ABSTRACT FROM AUTHOR]