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Updated: Sep 26, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Specification of CNS macrophage subsets occurs postnatally in defined niches
Takahiro Masuda1,2, Lukas Amann3, Gianni Monaco3
1Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. masuda@phar.kyushu-u.ac.jp.
Abstract:
All tissue-resident macrophages of the central nervous system (CNS)-including parenchymal microglia, as well as CNS-associated macrophages (CAMs1) such as meningeal and perivascular macrophages2-7-are part of the CNS endogenous innate immune system that acts as the first line of defence during infections or trauma2,8-10. It has been suggested that microglia and all subsets of CAMs are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors11-15. However, the precise ontogenetic relationships, the underlying transcriptional programs and the molecular signals that drive the development of distinct CAM subsets in situ are poorly understood. Here we show, using fate-mapping systems, single-cell profiling and cell-specific mutants, that only meningeal macrophages and microglia share a common prenatal progenitor. By contrast, perivascular macrophages originate from perinatal meningeal macrophages only after birth in an integrin-dependent manner. The establishment of perivascular macrophages critically requires the presence of arterial vascular smooth muscle cells. Together, our data reveal a precisely timed process in distinct anatomical niches for the establishment of macrophage subsets in the CNS.
Insights
Central nervous system (CNS) macrophages, including microglia and CNS-associated macrophages (CAMs), originate from distinct prenatal and perinatal sources. This study clarifies their developmental pathways and cellular origins within the CNS.
Area of Science:
- Neuroimmunology
- Developmental Biology
- Innate Immunity
Background:
- Tissue-resident macrophages, including microglia and CNS-associated macrophages (CAMs), are crucial for central nervous system (CNS) innate immunity.
- Previous research suggested a common prenatal yolk sac origin for all CNS macrophage subsets.
- The precise ontogenetic relationships and developmental signals for distinct CAM subsets remain poorly understood.
Purpose of the Study:
- To elucidate the developmental origins and relationships of distinct macrophage subsets within the CNS.
- To identify the molecular signals and cellular interactions governing the in situ development of CNS macrophages.
- To clarify the ontogeny of microglia, meningeal macrophages, and perivascular macrophages.
Main Methods:
- Utilized fate-mapping systems to trace cell lineages during CNS development.
- Employed single-cell profiling to analyze transcriptional programs of macrophage subsets.
- Generated and analyzed cell-specific mutants to investigate molecular requirements.
Main Results:
- Identified a shared prenatal progenitor for microglia and meningeal macrophages.
- Demonstrated that perivascular macrophages arise postnatally from meningeal macrophages in an integrin-dependent manner.
- Revealed that arterial vascular smooth muscle cells are essential for perivascular macrophage establishment.
Conclusions:
- CNS macrophage subsets originate from distinct prenatal and perinatal sources, challenging previous assumptions.
- The development of perivascular macrophages is a precisely timed, postnatal event dependent on specific cellular interactions.
- This study provides a detailed map of CNS macrophage ontogeny within distinct anatomical niches.
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