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

Zeynep Ilgin Kolabas, Louis B. Kuemmerle, Robert Perneczky, Benjamin Förstera, Selin Ulukaya, Mayar Ali, Saketh Kapoor, Laura M. Bartos, Maren Büttner, Ozum Sehnaz Caliskan, Zhouyi Rong, Hongcheng Mai, Luciano Höher, Denise Jeridi, Muge Molbay, Igor Khalin, Ioannis K. Deligiannis, Moritz Negwer, Kenny Roberts, Alba SimatsOlga Carofiglio, Mihail I. Todorov, Izabela Horvath, Furkan Ozturk, Selina Hummel, Gloria Biechele, Artem Zatcepin, Marcus Unterrainer, Johannes Gnörich, Jay Roodselaar, Joshua Shrouder, Pardis Khosravani, Benjamin Tast, Lisa Richter, Laura Díaz-Marugán, Doris Kaltenecker, Laurin Lux, Ying Chen, Shan Zhao, Boris Stephan Rauchmann, Michael Sterr, Ines Kunze, Karen Stanic, Vanessa W.Y. Kan, Simon Besson-Girard, Sabrina Katzdobler, Carla Palleis, Julia Schädler, Johannes C. Paetzold, Sabine Liebscher, Anja E. Hauser, Ozgun Gokce, Heiko Lickert, Hanno Steinke, Corinne Benakis, Christian Braun, Celia P. Martinez-Jimenez, Katharina Buerger, Nathalie L. Albert, Günter Höglinger, Johannes Levin, Christian Haass, Anna Kopczak, Martin Dichgans, Joachim Havla, Tania Kümpfel, Martin Kerschensteiner, Martina Schifferer, Mikael Simons, Arthur Liesz, Natalie Krahmer, Omer A. Bayraktar, Nicolai Franzmeier, Nikolaus Plesnila, Suheda Erener, Victor G. Puelles, Claire Delbridge, Harsharan Singh Bhatia, Farida Hellal, Markus Elsner, Ingo Bechmann, Benjamin Ondruschka, Matthias Brendel, Fabian J. Theis, Ali Erturk

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish
Pages (from-to)3706-3725.e29
JournalCell
Volume186
Issue number17
DOIs
StatePublished - 17 Aug 2023

Keywords

  • 3D-imaging
  • DISCO clearing
  • PET imaging
  • immune cell trafficking
  • neuroinflammation
  • neurological disorders
  • non-invasive monitoring
  • proteomics
  • scRNA-seq
  • skull-brain connection

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