Molecular anatomy of adult mouse leptomeninges

Riikka Pietilä; Francesca Del Gaudio; Liqun He; Elisa Vázquez-Liébanas; Michael Vanlandewijck; Lars Muhl; Giuseppe Mocci; Katrine D Bjørnholm; Caroline Lindblad; Alexander Fletcher-Sandersjöö; Mikael Svensson; Eric P Thelin; Jianping Liu; A Jantine van Voorden; Monica Torres; Salli Antila; Li Xin; Helena Karlström; Jon Storm-Mathisen; Linda Hildegard Bergersen; Aldo Moggio; Emil M Hansson; Maria H Ulvmar; Per Nilsson; Taija Mäkinen; Maarja Andaloussi Mäe; Kari Alitalo; Steven T Proulx; Britta Engelhardt; Donald M McDonald; Urban Lendahl; Johanna Andrae; Christer Betsholtz

doi:10.1016/j.neuron.2023.09.002

Molecular anatomy of adult mouse leptomeninges

Neuron. 2023 Dec 6;111(23):3745-3764.e7. doi: 10.1016/j.neuron.2023.09.002. Epub 2023 Sep 29.

Authors

Riikka Pietilä¹, Francesca Del Gaudio², Liqun He¹, Elisa Vázquez-Liébanas¹, Michael Vanlandewijck³, Lars Muhl⁴, Giuseppe Mocci⁴, Katrine D Bjørnholm⁵, Caroline Lindblad⁶, Alexander Fletcher-Sandersjöö⁷, Mikael Svensson⁸, Eric P Thelin⁸, Jianping Liu⁴, A Jantine van Voorden¹, Monica Torres¹, Salli Antila⁹, Li Xin¹⁰, Helena Karlström⁵, Jon Storm-Mathisen¹¹, Linda Hildegard Bergersen¹², Aldo Moggio¹³, Emil M Hansson¹³, Maria H Ulvmar¹⁴, Per Nilsson⁵, Taija Mäkinen¹, Maarja Andaloussi Mäe¹, Kari Alitalo⁹, Steven T Proulx¹⁰, Britta Engelhardt¹⁰, Donald M McDonald¹⁵, Urban Lendahl¹³, Johanna Andrae¹, Christer Betsholtz¹⁶

Affiliations

¹ Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden.
² Department of Medicine Huddinge, Karolinska Institutet, 14157 Huddinge, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
³ Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden; Department of Medicine Huddinge, Karolinska Institutet, 14157 Huddinge, Sweden.
⁴ Department of Medicine Huddinge, Karolinska Institutet, 14157 Huddinge, Sweden.
⁵ Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, 17177 Stockholm, Sweden.
⁶ Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden; Department of Neurosurgery, Uppsala University Hospital, 75185 Uppsala, Sweden; Department of Medical Sciences, Uppsala University, 75185 Uppsala, Sweden.
⁷ Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden; Department of Neurosurgery, Karolinska University Hospital, 17176 Stockholm, Sweden.
⁸ Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, 17176 Stockholm, Sweden.
⁹ Wihuri Research Institute and Translational Cancer Medicine Program, University of Helsinki, 00014 Helsinki, Finland.
¹⁰ Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
¹¹ Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
¹² Brain and Muscle Energy Group, Institute of Oral Biology, University of Oslo, 0316 Oslo, Norway; Center for Healthy Aging, Copenhagen University, 2200 Copenhagen, Denmark.
¹³ Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
¹⁴ Department of Medical Biochemistry and Microbiology, Uppsala University, 75123 Uppsala, Sweden.
¹⁵ Cardiovascular Research Institute, UCSF Helen Diller Family Comprehensive Cancer Center, and Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁶ Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden; Department of Medicine Huddinge, Karolinska Institutet, 14157 Huddinge, Sweden. Electronic address: christer.betsholtz@igp.uu.se.

PMID: 37776854
DOI: 10.1016/j.neuron.2023.09.002

Abstract

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.

Keywords: arachnoid barrier; arachnoid mater; brain fibroblasts; dura mater; leptomeninges; perivascular fibroblast; pia mater; single-cell RNA sequencing; traumatic brain injury; tricellular junction.

MeSH terms

Animals
Arachnoid* / anatomy & histology
Brain
Choroid Plexus
Meninges*
Mice
Pia Mater