Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge
Abstract: Microglia are yolk sac-derived macrophages residing in the parenchyma of brain and spinal cord, where they interact with neurons and other glial. After different conditioning paradigms and bone marrow (BM) or hematopoietic stem cell (HSC) transplantation, graft-derived cells seed the brain and persistently contribute to the parenchymal brain macrophage compartment. Here we establish that graft-derived macrophages acquire, over time, microglia characteristics, including ramified morphology, longevity, radio-resistance and clonal expansion. However, even after prolonged CNS residence, transcriptomes and chromatin accessibility landscapes of engrafted, BM-derived macrophages remain distinct from yolk sac-derived host microglia. Furthermore, engrafted BM-derived cells display discrete responses to peripheral endotoxin challenge, as compared to host microglia. In human HSC transplant recipients, engrafted cells also remain distinct from host microglia, extending our finding to clinical settings. Collectively, our data emphasize the molecular and functional heterogeneity of parenchymal brain macrophages and highlight potential clinical implications for HSC gene therapies aimed to ameliorate lysosomal storage disorders, microgliopathies or general monogenic immuno-deficiencies
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Notes
-
Nature communications. - 9, 1 (2018) , 5206, ISSN: 2041-1723
- Event
-
Veröffentlichung
- (where)
-
Freiburg
- (who)
-
Universität
- (when)
-
2019
- Creator
-
Shemer, Anat
Grozovski, Jonathan
Tuan, Leng-Tay
Tao, Jenhan
Volaski, Alon
Süß, Patrick
Ardura-Fabregat, Alberto
Gross-Vered, Mor
Kim, Jung-Seok
David, Eyal
Chappell-Maor, Louise
Thielecke, Lars
Glass, Christopher K.
Cornils, Kerstin
Prinz, Marco
Jung, Steffen
- Contributor
- DOI
-
10.1038/s41467-018-07548-5
- URN
-
urn:nbn:de:bsz:25-freidok-1477688
- Rights
-
Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
- 14.08.2025, 10:48 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Shemer, Anat
- Grozovski, Jonathan
- Tuan, Leng-Tay
- Tao, Jenhan
- Volaski, Alon
- Süß, Patrick
- Ardura-Fabregat, Alberto
- Gross-Vered, Mor
- Kim, Jung-Seok
- David, Eyal
- Chappell-Maor, Louise
- Thielecke, Lars
- Glass, Christopher K.
- Cornils, Kerstin
- Prinz, Marco
- Jung, Steffen
- Albert-Ludwigs-Universität Freiburg. Entwicklungsbiologie
- Universität
Time of origin
- 2019
Other Objects (12)
Morphometrie und Ontogenese von Interneuronen des Gyrus praecentralis peri- und postnataler Entwicklungsstufen des Menschen
Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge
Microglia: same same, but different
Microglia out of place—mapping macrophages across the developing human body
Life and death of microglia: Mechanisms governing microglial states and fates
Microglia out of place—mapping macrophages across the developing human body
The roles of microglia in viral encephalitis: from sensome to therapeutic targeting
Somatic mosaicism in microglia - a model for neurodegeneration in histiocytosis and implications for treatment
Microglia heterogeneity in the single-cell era
Funktion des Glukose-6-Phosphat-Transporters SLC37A2 und die Rekrutierungsmechanismen myeloider Zellen ins Zentrale Nervensystem
Immune checkpoint inhibitor induced neurocognitive deficits in patients
NF-[kappa] B signaling regulates myelination in the CNS
Morphometrie und Ontogenese von Interneuronen des Gyrus praecentralis peri- und postnataler Entwicklungsstufen des Menschen
Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge
Microglia: same same, but different
Microglia out of place—mapping macrophages across the developing human body
Life and death of microglia: Mechanisms governing microglial states and fates
Microglia out of place—mapping macrophages across the developing human body
The roles of microglia in viral encephalitis: from sensome to therapeutic targeting
Somatic mosaicism in microglia - a model for neurodegeneration in histiocytosis and implications for treatment
Microglia heterogeneity in the single-cell era
Funktion des Glukose-6-Phosphat-Transporters SLC37A2 und die Rekrutierungsmechanismen myeloider Zellen ins Zentrale Nervensystem
Immune checkpoint inhibitor induced neurocognitive deficits in patients
NF-[kappa] B signaling regulates myelination in the CNS
Morphometrie und Ontogenese von Interneuronen des Gyrus praecentralis peri- und postnataler Entwicklungsstufen des Menschen
Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge
Microglia: same same, but different
Microglia out of place—mapping macrophages across the developing human body
Life and death of microglia: Mechanisms governing microglial states and fates
Microglia out of place—mapping macrophages across the developing human body
The roles of microglia in viral encephalitis: from sensome to therapeutic targeting
Somatic mosaicism in microglia - a model for neurodegeneration in histiocytosis and implications for treatment
Microglia heterogeneity in the single-cell era
Funktion des Glukose-6-Phosphat-Transporters SLC37A2 und die Rekrutierungsmechanismen myeloider Zellen ins Zentrale Nervensystem
Immune checkpoint inhibitor induced neurocognitive deficits in patients