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Fig. 2 | Inflammation and Regeneration

Fig. 2

From: Neuroplasticity related to chronic pain and its modulation by microglia

Fig. 2

The origin of tissue-resident macrophages (microglia, perivascular/ meningeal/ choroid plexus macrophage) in the CNS. Tissue-resident macrophages of the CNS in mammals are derived from three consecutive hematopoietic systems (primitive hematopoiesis, transient-definitive hematopoiesis, definitive hematopoiesis) during embryogenesis. In mouse primitive hematopoiesis, erythro-myeloid progenitors (EMPs) occur in the yolk sac of extraembryonic tissue during the embryonic period (E7-7.5), and primitive macrophages are produced from these EMPs independently of the transcription factor Myb without going through monocytes. Primitive macrophages are then carried to each organ by the circulatory system and engrafted before the formation of the blood-brain barrier. Microglia in the parenchyma of the brain and spinal cord differentiate from these primitive macrophages. Around E9.5, yolk sac-derived EMPs migrate from the yolk sac to the fetal liver and initiate transient-definitive hematopoiesis. Then, in transient-definitive hematopoiesis, monocytes are produced from EMPs in a Myb-dependent manner, and the primitive macrophages previously engrafted in each organ are replaced. Since the blood-brain barrier is formed in the brain and infiltration of these monocytes rarely occurs, only microglia present in the parenchyma of the brain and spinal cord are the main origins of primitive macrophages derived in the yolk sac. Around E10.5, hematopoietic stem cells (HSCs) migrate to the fetal liver to start definitive hematopoiesis. HSCs migrate from the fetal liver to the bone marrow before birth and supply the entire line of blood cells throughout life. Choroid plexus macrophages derive from HSC-EMP or blood monocytes. Below the dotted line, microglia and CNS tissue-resident macrophages, and common gene expression patterns are shown

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