Multi-omics and 3D-imaging reveal bone heterogeneity and unique calvaria cells in neuroinflammation
Author:
Kolabas Zeynep Ilgin, Kuemmerle Louis B., Perneczky RobertORCID, Förstera Benjamin, Büttner MarenORCID, Caliskan Ozum Sehnaz, Ali Mayar, Rong Zhouyi, Mai Hongcheng, Hummel Selina, Bartos Laura M., Biechele Gloria, Zatcepin Artem, Albert Natalie L., Unterrainer Marcus, Gnörich Johannes, Zhao Shan, Khalin Igor, Rauchmann Boris-Stephan, Molbay Muge, Sterr Michael, Kunze Ines, Stanic Karen, Besson-Girard Simon, Kopczak Anna, Katzdobler Sabrina, Palleis Carla, Gokce Ozgun, Lickert Heiko, Steinke Hanno, Bechmann Ingo, Buerger Katharina, Levin Johannes, Haass Christian, Dichgans Martin, Havla JoachimORCID, Kümpfel Tania, Kerschensteiner Martin, Simons Mikael, Plesnila Nikolaus, Krahmer Natalie, Bhatia Harsharan Singh, Erener Suheda, Hellal Farida, Brendel Matthias, Theis Fabian J., Erturk Ali
Abstract
SUMMARYThe meninges of the brain are an important component of neuroinflammatory response. Diverse immune cells move from the calvaria marrow into the dura mater via recently discovered skull-meninges connections (SMCs). However, how the calvaria bone marrow is different from the other bones and whether and how it contributes to human diseases remain unknown. Using multi-omics approaches and whole mouse transparency we reveal that bone marrow cells are highly heterogeneous across the mouse body. The calvaria harbors the most distinct molecular signature with hundreds of differentially expressed genes and proteins. Acute brain injury induces skull-specific alterations including increased calvaria cell numbers. Moreover, TSPO-positron-emission-tomography imaging of stroke, multiple sclerosis and neurodegenerative disease patients demonstrate disease-associated uptake patterns in the human skull, mirroring the underlying brain inflammation. Our study indicates that the calvaria is more than a physical barrier, and its immune cells may present new ways to control brain pathologies.Graphical AbstractHighlightsBone marrow across the mouse body display heterogeneity in their molecular profileCalvaria cells have a distinct profile that is relevant to brain pathologiesBrain native proteins are identified in calvaria in pathological statesTSPO-PET imaging of the human skull can be a proxy of neuroinflammation in the brainSupplementary Videos can be seen at: http://discotechnologies.org/Calvaria/
Publisher
Cold Spring Harbor Laboratory
Cited by
12 articles.
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