ArticleJournal of neuroinflammation2020
Effects of long-term and brain-wide colonization of peripheral bone marrow-derived myeloid cells in the CNS.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
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- Enhancing the specificity of microglia genetic targeting using a CSF1R inhibitor.Cell reports · 2026Article
- Characterization of effects of a neurotropic murine coronavirus infection on Alzheimer's disease neuropathology of 5xFAD mice.bioRxiv : the preprint server for biology · 2026Article
- Toxoplasma gondii drives myeloid immune cell recruitment to amyloid plaques in Alzheimer's model mice.Journal of neuroinflammation · 2026Article
- The senescent niche hypothesis: microglial dysfunction and replacement strategies in drug-resistant epilepsy.Frontiers in immunology · 2026Review
- Basic Microglial Functions and How They Go Awry in Neurodegenerative Disease.Annual review of pathology · 2026Review
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- From sentinels to engineers: The future of microglia in brain regeneration.Cell stem cell · 2025Article
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- Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health.Nature communications · 2025Article
- Identification of the velum interpositum as a meningeal-CNS route for myeloid cell trafficking into the brain.Neuron · 2025Article
- Role of MS4A7 in Regulating Microglial Polarization and Neuroinflammation in Spinal Cord Injury via the cGAS-STING-NLRP3 Axis.CNS neuroscience & therapeutics · 2025Article
- Monocyte-derived macrophages act as reinforcements when microglia fall short in Alzheimer's disease.Nature neuroscience · 2025Review
- Article
- Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.bioRxiv : the preprint server for biology · 2024Article
- Therapeutic efficacy of intracerebral hematopoietic stem cell gene therapy in an Alzheimer's disease mouse model.Nature communications · 2024Article
- CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice.Nature communications · 2024Article
- Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis.Nature neuroscience · 2024Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMicroglia, the primary resident myeloid cells of the brain, play critical roles in immune defense by maintaining tissue homeostasis and responding to injury or disease. However, microglial activation and dysfunction has been implicated in a number of central nervous system (CNS) disorders, thus developing tools to manipulate and replace these myeloid cells in the CNS is of therapeutic interest.
methodsUsing whole body irradiation, bone marrow transplant, and colony-stimulating factor 1 receptor inhibition, we achieve long-term and brain-wide (~ 80%) engraftment and colonization of peripheral bone marrow-derived myeloid cells (i.e., monocytes) in the brain parenchyma and evaluated the long-term effects of their colonization in the CNS.
resultsHere, we identify a monocyte signature that includes an upregulation in Ccr1, Ms4a6b, Ms4a6c, Ms4a7, Apobec1, Lyz2, Mrc1, Tmem221, Tlr8, Lilrb4a, Msr1, Nnt, and Wdfy1 and a downregulation of Siglech, Slc2a5, and Ccl21a/b. We demonstrate that irradiation and long-term (~ 6 months) engraftment of the CNS by monocytes induces brain region-dependent alterations in transcription profiles, astrocytes, neuronal structures, including synaptic components, and cognition. Although our results show that microglial replacement with peripherally derived myeloid cells is feasible and that irradiation-induced changes can be reversed by the replacement of microglia with monocytes in the hippocampus, we also observe that brain-wide engraftment of peripheral myeloid cells (relying on irradiation) can result in cognitive and synaptic deficits.
conclusionsThese findings provide insight into better understanding the role and complexity of myeloid cells in the brain, including their regulation of other CNS cells and functional outcomes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.