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Distinct molecular profiles of skull bone marrow in health and neurological disorders.
Cell 186, 3706-3725.e29 (2023)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
3d-imaging ; Disco Clearing ; Pet Imaging ; Immune Cell Trafficking ; Neuroinflammation ; Neurological Disorders ; Non-invasive Monitoring ; Proteomics ; Scrna-seq ; Skull-brain Connection; Enrichment Analysis; Ischemic-stroke; Web Server; Reveals; Brain; Activation; Protein; Cells; Pet; Deposition
ISSN (print) / ISBN
0092-8674
e-ISSN
1097-4172
Zeitschrift
Cell
Quellenangaben
Band: 186,
Heft: 17,
Seiten: 3706-3725.e29
Verlag
Cell Press
Verlagsort
Cambridge, Mass.
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute for Tissue Engineering and Regenerative Medicine (ITERM)
Institute of Computational Biology (ICB)
Institute of Diabetes and Obesity (IDO)
Helmholtz Pioneer Campus (HPC)
Institute of Diabetes and Cancer (IDC)
Institute of Diabetes and Regeneration Research (IDR)
Institute of Stem Cell Research (ISF)
Institute of Computational Biology (ICB)
Institute of Diabetes and Obesity (IDO)
Helmholtz Pioneer Campus (HPC)
Institute of Diabetes and Cancer (IDC)
Institute of Diabetes and Regeneration Research (IDR)
Institute of Stem Cell Research (ISF)
Förderungen
Nomis Foundation
Vascular Dementia Research Foundation
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Friedrich-Baur-Stiftung
Luneburg Heritage Foundation
European Research Council (ERC)
Einstein Foundation Berlin
Novo Nordisk Foundation
National Institute for Health and Care Research (NIHR) Sheffield Biomedical Research Centre
Hirnliga e.V
Alzheimer Forschung Initiative
BMBF
NATON collaboration of the Network University Medicine
EMed Consortia "Fibromap."
Vascular Dementia Research Foundation
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Friedrich-Baur-Stiftung
Luneburg Heritage Foundation
European Research Council (ERC)
Einstein Foundation Berlin
Novo Nordisk Foundation
National Institute for Health and Care Research (NIHR) Sheffield Biomedical Research Centre
Hirnliga e.V
Alzheimer Forschung Initiative
BMBF
NATON collaboration of the Network University Medicine
EMed Consortia "Fibromap."