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| Home > Publications Database > Distinct molecular profiles of skull bone marrow in health and neurological disorders. |
| Home > Publications Database > Distinct molecular profiles of skull bone marrow in health and neurological disorders. |
| Journal Article | DZNE-2023-00812 |
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2023
Elsevier
New York, NY
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Please use a persistent id in citations: doi:10.1016/j.cell.2023.07.009
Abstract: 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.
Keyword(s): Nervous System Diseases: pathology (MeSH) ; Mice (MeSH) ; Animals (MeSH) ; Humans (MeSH) ; Bone Marrow: metabolism (MeSH) ; Skull: diagnostic imaging (MeSH) ; Brain: diagnostic imaging (MeSH) ; Brain: metabolism (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Nervous System Diseases: genetics (MeSH) ; Nervous System Diseases: metabolism (MeSH) ; Carrier Proteins: metabolism (MeSH) ; Receptors, GABA: metabolism (MeSH) ; Skull: cytology (MeSH) ; 3D-imaging ; DISCO clearing ; PET imaging ; immune cell trafficking ; neuroinflammation ; neurological disorders ; non-invasive monitoring ; proteomics ; scRNA-seq ; skull-brain connection ; Carrier Proteins ; Receptors, GABA ; TSPO protein, human
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