Molecular anatomy of adult mouse leptomeninges

• Published in: Neuron (Cambridge, Mass.) Vol. 111; no. 23; pp. 3745 - 3764.e7
• Main Authors: Pietilä, Riikka, Del Gaudio, Francesca, He, Liqun, Vázquez-Liébanas, Elisa, Vanlandewijck, Michael, Muhl, Lars, Mocci, Giuseppe, Bjørnholm, Katrine D., Lindblad, Caroline, Fletcher-Sandersjöö, Alexander, Svensson, Mikael, Thelin, Eric P., Liu, Jianping, van Voorden, A. Jantine, Torres, Monica, Antila, Salli, Xin, Li, Karlström, Helena, Storm-Mathisen, Jon, Bergersen, Linda Hildegard, Moggio, Aldo, Hansson, Emil M., Ulvmar, Maria H., Nilsson, Per, Mäkinen, Taija, Andaloussi Mäe, Maarja, Alitalo, Kari, Proulx, Steven T., Engelhardt, Britta, McDonald, Donald M., Lendahl, Urban, Andrae, Johanna, Betsholtz, Christer
• Format: Journal Article
• Language: English
• Published: United States 06.12.2023
• Subjects: arachnoid barrier; brain fibroblasts; single-cell RNA sequencing; pia mater; tricellular junction; perivascular fibroblast; arachnoid mater; leptomeninges; traumatic brain injury; dura mater
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2023.09.002

Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.