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Genes Dev. 2021 Aug 01;35(15):1190-1207. doi: 10.1101/gad.348190.120. Epub 2021 Jul 22.

Single-cell atlas reveals meningeal leukocyte heterogeneity in the developing mouse brain.

Genes & development

Aura Zelco, Vanja Börjesson, Jurrian K de Kanter, Cristina Lebrero-Fernandez, Volker M Lauschke, Eridan Rocha-Ferreira, Gisela Nilsson, Syam Nair, Pernilla Svedin, Mats Bemark, Henrik Hagberg, Carina Mallard, Frank C P Holstege, Xiaoyang Wang

Affiliations

  1. Centre of Perinatal Medicine and Health, Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden.
  2. Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg 413 90, Sweden.
  3. Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.
  4. Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden.
  5. Department of Physiology and Pharmacology, Karolinska Institute, Stockholm 17177, Sweden.
  6. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart 70 376, Germany.
  7. Centre of Perinatal Medicine and Health, Institute of Clinical Sciences, Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg University, Gothenburg 40530, Sweden.
  8. Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

PMID: 34301765 PMCID: PMC8336895 DOI: 10.1101/gad.348190.120

Abstract

The meninges are important for brain development and pathology. Using single-cell RNA sequencing, we have generated the first comprehensive transcriptional atlas of neonatal mouse meningeal leukocytes under normal conditions and after perinatal brain injury. We identified almost all known leukocyte subtypes and found differences between neonatal and adult border-associated macrophages, thus highlighting that neonatal border-associated macrophages are functionally immature with regards to immune responses compared with their adult counterparts. We also identified novel meningeal microglia-like cell populations that may participate in white matter development. Early after the hypoxic-ischemic insult, neutrophil numbers increased and they exhibited increased granulopoiesis, suggesting that the meninges are an important site of immune cell expansion with implications for the initiation of inflammatory cascades after neonatal brain injury. Our study provides a single-cell resolution view of the importance of meningeal leukocytes at the early stage of development in health and disease.

© 2021 Zelco et al.; Published by Cold Spring Harbor Laboratory Press.

Keywords: meningeal leukocytes; neonatal mouse; preterm brain injury; single-cell RNA sequencing

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