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Updated: Jul 10, 2026
Obtaining Human Microglia from Adult Human Brain Tissue
Published on: August 30, 2020
Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
Alexander Mildner1, Hauke Schmidt, Mirko Nitsche
1Institute of Neuropathology, Georg August University, Göttingen, Germany.
Abstract:
Microglia are crucially important myeloid cells in the CNS and constitute the first immunological barrier against pathogens and environmental insults. The factors controlling microglia recruitment from the blood remain elusive and the direct circulating microglia precursor has not yet been identified in vivo. Using a panel of bone marrow chimeric and adoptive transfer experiments, we found that circulating Ly-6C(hi)CCR2(+) monocytes were preferentially recruited to the lesioned brain and differentiated into microglia. Notably, microglia engraftment in CNS pathologies, which are not associated with overt blood-brain barrier disruption, required previous conditioning of brain (for example, by direct tissue irradiation). Our results identify Ly-6C(hi)CCR2(+) monocytes as direct precursors of microglia in the adult brain and establish the importance of local factors in the adult CNS for microglia engraftment.
Insights
Circulating monocytes are the direct precursors of microglia in the adult brain. Brain conditioning is essential for microglia engraftment in central nervous system pathologies, highlighting the role of local factors.
Area of Science:
- Neuroimmunology
- Central Nervous System (CNS) Immunity
- Hematopoietic Cell Differentiation
Background:
- Microglia are vital myeloid cells in the CNS, forming the primary immune defense.
- Mechanisms of microglia recruitment and their circulating precursors in vivo are not well understood.
Purpose of the Study:
- To identify the circulating precursors of microglia in the adult brain.
- To investigate the factors influencing microglia engraftment in the CNS.
Main Methods:
- Bone marrow chimeric experiments
- Adoptive transfer studies
- In vivo tracking of monocyte and microglia populations
Main Results:
- Circulating Ly-6C(hi)CCR2(+) monocytes were preferentially recruited to lesioned brain sites.
- These monocytes differentiated into microglia within the CNS.
- Microglia engraftment in non-disrupted CNS pathologies required prior brain conditioning, such as irradiation.
Conclusions:
- Ly-6C(hi)CCR2(+) monocytes serve as direct precursors for microglia in the adult brain.
- Local CNS factors and brain conditioning are critical for microglia engraftment, particularly in pathological conditions.
