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

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

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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. Weidentified 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.

Original languageEnglish
Pages (from-to)1190-1207
Number of pages18
JournalGenes and Development
Volume35
Issue number15-16
DOIs
Publication statusPublished - 1 Aug 2021

Keywords

  • Meningeal leukocytes
  • Neonatal mouse
  • Preterm brain injury
  • Single-cell RNA sequencing

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