Distinct molecular profiles of skull bone marrow in health and neurological disorders
Zeynep Ilgin Kolabas(Helmholtz Zentrum München), Louis B. Kuemmerle(Helmholtz Zentrum München), Robert Perneczky(German Center for Neurodegenerative Diseases), Benjamín Förstera(Helmholtz Zentrum München), Selin Ulukaya(Helmholtz Zentrum München), Mayar Ali(Helmholtz Zentrum München), Saketh Kapoor(Helmholtz Zentrum München), Laura M. Bartos(Ludwig-Maximilians-Universität München), Maren Büttner(Helmholtz Zentrum München), Özüm Şehnaz Çalışkan(Deutsches Diabetes-Zentrum e.V.), Zhouyi Rong(Helmholtz Zentrum München), Hongcheng Mai(Helmholtz Zentrum München), Luciano Höher(Helmholtz Zentrum München), Denise Jeridi(Helmholtz Zentrum München), Müge Molbay(Helmholtz Zentrum München), Igor Khalin(Ludwig-Maximilians-Universität München), Ioannis K. Deligiannis(Helmholtz Zentrum München), Moritz Negwer(Helmholtz Zentrum München), Kenny Roberts(Wellcome Sanger Institute), Alba Simats(Ludwig-Maximilians-Universität München), Olga Carofiglio(Ludwig-Maximilians-Universität München), Mihail Ivilinov Todorov(Helmholtz Zentrum München), Izabela Horvath(Helmholtz Zentrum München), Furkan Öztürk(Helmholtz Zentrum München), Selina Hummel(German Center for Neurodegenerative Diseases), Gloria Biechele(Ludwig-Maximilians-Universität München), Artem Zatcepin(German Center for Neurodegenerative Diseases), Marcus Unterrainer(LMU Klinikum), Johannes Gnörich(Ludwig-Maximilians-Universität München), Jay Roodselaar(German Rheumatism Research Centre), Joshua Shrouder(Ludwig-Maximilians-Universität München), Pardis Khosravani(Ludwig-Maximilians-Universität München), Benjamin Tast(Ludwig-Maximilians-Universität München), Lisa Richter(Ludwig-Maximilians-Universität München), Laura Díaz-Marugán(Ludwig-Maximilians-Universität München), Doris Kaltenecker(Helmholtz Zentrum München), Laurin Lux(Helmholtz Zentrum München), Ying Chen(Ludwig-Maximilians-Universität München), Shan Zhao(Helmholtz Zentrum München), Boris‐Stephan Rauchmann(LMU Klinikum), Michael Sterr(Helmholtz Zentrum München), Ines Kunze(Helmholtz Zentrum München), Karen Stanic(Helmholtz Zentrum München), Vanessa W. Y. Kan(Ludwig-Maximilians-Universität München), Simon Besson‐Girard(Ludwig-Maximilians-Universität München), Sabrina Katzdobler(German Center for Neurodegenerative Diseases), Carla Palleis(German Center for Neurodegenerative Diseases), Julia Schädler(Universität Hamburg), Johannes C. Paetzold(Helmholtz Zentrum München), Sabine Liebscher(Munich Cluster for Systems Neurology), Anja E. Hauser(German Rheumatism Research Centre), Özgün Gökçe(Munich Cluster for Systems Neurology), Heiko Lickert(Helmholtz Zentrum München), Hanno Steinke(Leipzig University), Corinne Benakis(Ludwig-Maximilians-Universität München), C. Braun(Ludwig-Maximilians-Universität München), Celia Pilar Martinez‐Jimenez(Helmholtz Zentrum München), Katharina Büerger(German Center for Neurodegenerative Diseases), Nathalie L. Albert(Ludwig-Maximilians-Universität München), Günter U. Höglinger(German Center for Neurodegenerative Diseases), Johannes Levin(German Center for Neurodegenerative Diseases), Christian Haass(German Center for Neurodegenerative Diseases), Anna Kopczak(Ludwig-Maximilians-Universität München), Martin Dichgans(German Center for Neurodegenerative Diseases), Joachim Havla(Ludwig-Maximilians-Universität München), Tania Kümpfel(Ludwig-Maximilians-Universität München), Martin Kerschensteiner(Munich Cluster for Systems Neurology), Martina Schifferer(German Center for Neurodegenerative Diseases), Mikael Simons(German Center for Neurodegenerative Diseases), Arthur Liesz(Munich Cluster for Systems Neurology), Natalie Krahmer(Deutsches Diabetes-Zentrum e.V.), Omer Ali Bayraktar(Wellcome Sanger Institute), Nicolai Franzmeier(Ludwig-Maximilians-Universität München), Nikolaus Plesnila(Munich Cluster for Systems Neurology), Süheda Erener(Helmholtz Zentrum München), Victor G. Puelles(Universität Hamburg), Claire Delbridge(Technical University of Munich), Harsharan S. Bhatia(Helmholtz Zentrum München), Farida Hellal(Helmholtz Zentrum München), Markus Elsner(Helmholtz Zentrum München), Ingo Bechmann(Leipzig University), Benjamin Ondruschka(Universität Hamburg), Matthias Brendel(German Center for Neurodegenerative Diseases), Fabian J. Theis(Helmholtz Zentrum München), Ali Ertürk(Helmholtz Zentrum München)
Cited by 151Open Access
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.