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Updated: Jun 27, 2026

Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Brain-Engrafted Monocyte-derived Macrophages from Blood and Skull-Bone Marrow Exhibit Distinct Identities from
Abstract:
Microglia are thought to originate exclusively from primitive macrophage progenitors in the yolk sac (YS) and to persist throughout life without much contribution from definitive hematopoiesis. Here, using lineage tracing, pharmacological manipulation, and RNA-sequencing, we elucidated the presence and characteristics of monocyte-derived macrophages (MDMs) in the brain parenchyma at baseline and during microglia repopulation, and defined the core transcriptional signatures of brain-engrafted MDMs. Lineage tracing mouse models revealed that MDMs transiently express CD206 during brain engraftment as CD206 + microglia precursors in the YS. We found that brain-engrafted MDMs exhibit transcriptional and epigenetic characteristics akin to meningeal macrophages, likely due to environmental imprinting within the meningeal space. Utilizing parabiosis and skull transplantation, we demonstrated that monocytes from both peripheral blood and skull bone marrow can repopulate microglia-depleted brains. Our results reveal the heterogeneous origins and cellular dynamics of brain parenchymal macrophages at baseline and in models of microglia depletion.
Insights
Monocyte-derived macrophages (MDMs) can enter the brain parenchyma, exhibiting unique transcriptional signatures and contributing to microglia repopulation. This challenges the notion of microglia
Area of Science:
- Neuroimmunology
- Hematopoiesis
- Cellular Dynamics
Background:
- Microglia were traditionally believed to originate solely from yolk sac (YS) progenitors and remain largely unchanged throughout life.
- The contribution of definitive hematopoiesis, particularly monocytes, to the brain's macrophage population was poorly understood.
Purpose of the Study:
- To investigate the presence, characteristics, and origins of monocyte-derived macrophages (MDMs) in the brain parenchyma.
- To define the transcriptional signatures of brain-engrafted MDMs and understand their dynamics during microglia repopulation.
Main Methods:
- Lineage tracing mouse models to track cell origins.
- Pharmacological manipulation to study repopulation dynamics.
- RNA-sequencing to define transcriptional signatures.
- Parabiosis and skull transplantation experiments.
Main Results:
- Monocyte-derived macrophages (MDMs) were identified in the brain parenchyma at baseline and during repopulation.
- Brain-engrafted MDMs share transcriptional and epigenetic similarities with meningeal macrophages, suggesting environmental imprinting.
- Both peripheral blood monocytes and skull bone marrow monocytes can repopulate microglia-depleted brains.
Conclusions:
- The brain parenchyma harbors heterogeneous macrophage populations with diverse origins, including monocytes.
- Microglia depletion can be repopulated by monocytes, challenging the exclusive yolk sac origin model.
- Understanding these cellular dynamics is crucial for neuroimmunological research and therapeutic strategies.
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