德国慕尼黑大学Ali Erturk团队揭示颅骨骨髓在健康和神经系统疾病中的不同分子特征。相关论文于2023年8月9日在线发表在《细胞》杂志上。
研究人员发现小鼠头骨与其他骨骼相比,在健康和损伤状态下具有最独特的转录组特征,其特点是中性粒细胞表型处于晚期。在人类中,蛋白质组分析表明颅骨骨髓是最独特的,具有不同表达的中性粒细胞相关通路和独特的突触蛋白特征。三维成像显示了与静脉相比,人类颅骨-脑膜连接(SMC)的结构和细胞细节。
最后,研究人员利用转运蛋白正电子发射断层扫描(TSPO-PET)成像技术显示,颅骨骨髓反映了各种神经系统疾病患者的脑部炎症反应,并具有疾病特异性的空间分布。颅骨独特的分子特征以及解剖和功能上的联系显示了其作为诊断、监测和治疗脑部疾病场所的潜力。
研究人员表示,颅骨中的骨髓对形成大脑和脑膜的免疫反应非常重要,但其在骨骼中的分子构成以及与人类疾病的相关性仍不清楚。
附:英文原文
Title: Distinct molecular profiles of skull bone marrow in health and neurological disorders
Author: Zeynep Ilgin Kolabas, Louis B. Kuemmerle, Robert Perneczky, Benjamin Frstera, Selin Ulukaya, Mayar Ali, Saketh Kapoor, Laura M. Bartos, Maren Büttner, Ozum Sehnaz Caliskan, Zhouyi Rong, Hongcheng Mai, Luciano Hher, Denise Jeridi, Muge Molbay, Igor Khalin, Ioannis K. Deligiannis, Moritz Negwer, Kenny Roberts, Alba Simats, Olga Carofiglio, Mihail I. Todorov, Izabela Horvath, Furkan Ozturk, Selina Hummel, Gloria Biechele, Artem Zatcepin, Marcus Unterrainer, Johannes Gnrich, 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 Schdler, Johannes C. Paetzold, Sabine Liebscher, Anja E. Hauser, Ozgun Gokce, Heiko Lickert, Hanno Steinke, Corinne Benakis, Christian Braun, Celia P. Martinez-Jimenez
Issue&Volume: 2023-08-09
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.
DOI: 10.1016/j.cell.2023.07.009
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00742-0