Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1042840 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Microglia arise from yolk sac progenitors and are thought to persist throughout life with minimal input from adult hematopoiesis. However, whether brain-engrafted monocyte-derived macrophages (MDM) exist at homeostasis and during turnover, and how they function relative to yolk sac-derived microglia (YSM) remain unsettled. Here, we combine lineage tracing, pharmacological microglia depletion, and multi-omics profiling to define the ontogeny, identity, and function of brain parenchymal macrophages. Despite sharing the parenchymal milieu, MDM display transcriptional and epigenetic landscapes distinct from YSM. Fate-mapping reveals that brain-engrafted MDM transiently express CD206, echoing a developmental stage of microglial precursors. MDM engraftment and polarization are modulated by IL-34 and CCR2. Furthermore, parabiosis and skull‑flap transplantation reveal that both blood and skull marrow supply the niche, yielding origin‑biased MDM states. Functionally, MDM engraftment enhanced cuprizone-mediated demyelination. Together, our study defines the origins, molecular features, and context-dependent roles of brain parenchymal macrophages across homeostasis, turnover, and CNS pathology.
2026-03-11 | GSE319243 | GEO
Project description:Microglia arise from yolk sac progenitors and are thought to persist throughout life with minimal input from adult hematopoiesis. However, whether brain-engrafted monocyte-derived macrophages (MDM) exist at homeostasis and during turnover, and how they function relative to yolk sac-derived microglia (YSM) remain unsettled. Here, we combine lineage tracing, pharmacological microglia depletion, and multi-omics profiling to define the ontogeny, identity, and function of brain parenchymal macrophages. Despite sharing the parenchymal milieu, MDM display transcriptional and epigenetic landscapes distinct from YSM. Fate-mapping reveals that brain-engrafted MDM transiently express CD206, echoing a developmental stage of microglial precursors. MDM engraftment and polarization are modulated by IL-34 and CCR2. Furthermore, parabiosis and skull‑flap transplantation reveal that both blood and skull marrow supply the niche, yielding origin‑biased MDM states. Functionally, MDM engraftment enhanced cuprizone-mediated demyelination. Together, our study defines the origins, molecular features, and context-dependent roles of brain parenchymal macrophages across homeostasis, turnover, and CNS pathology.
2026-03-11 | GSE319167 | GEO
Project description:Microglia arise from yolk sac progenitors and are thought to persist throughout life with minimal input from adult hematopoiesis. However, whether brain-engrafted monocyte-derived macrophages (MDM) exist at homeostasis and during turnover, and how they function relative to yolk sac-derived microglia (YSM) remain unsettled. Here, we combine lineage tracing, pharmacological microglia depletion, and multi-omics profiling to define the ontogeny, identity, and function of brain parenchymal macrophages. Despite sharing the parenchymal milieu, MDM display transcriptional and epigenetic landscapes distinct from YSM. Fate-mapping reveals that brain-engrafted MDM transiently express CD206, echoing a developmental stage of microglial precursors. MDM engraftment and polarization are modulated by IL-34 and CCR2. Furthermore, parabiosis and skull‑flap transplantation reveal that both blood and skull marrow supply the niche, yielding origin‑biased MDM states. Functionally, MDM engraftment enhanced cuprizone-mediated demyelination. Together, our study defines the origins, molecular features, and context-dependent roles of brain parenchymal macrophages across homeostasis, turnover, and CNS pathology.
2026-03-11 | GSE320070 | GEO
Project description:Microglia arise from yolk sac progenitors and are thought to persist throughout life with minimal input from adult hematopoiesis. However, whether brain-engrafted monocyte-derived macrophages (MDM) exist at homeostasis and during turnover, and how they function relative to yolk sac-derived microglia (YSM) remain unsettled. Here, we combine lineage tracing, pharmacological microglia depletion, and multi-omics profiling to define the ontogeny, identity, and function of brain parenchymal macrophages. Despite sharing the parenchymal milieu, MDM display transcriptional and epigenetic landscapes distinct from YSM. Fate-mapping reveals that brain-engrafted MDM transiently express CD206, echoing a developmental stage of microglial precursors. MDM engraftment and polarization are modulated by IL-34 and CCR2. Furthermore, parabiosis and skull‑flap transplantation reveal that both blood and skull marrow supply the niche, yielding origin‑biased MDM states. Functionally, MDM engraftment enhanced cuprizone-mediated demyelination. Together, our study defines the origins, molecular features, and context-dependent roles of brain parenchymal macrophages across homeostasis, turnover, and CNS pathology.
2026-03-11 | GSE319708 | GEO
Project description:Mouse 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 microglial precursors. 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 functional dynamics of brain parenchymal macrophages at baseline and in models of microglia depletion.
2026-07-31 | GSE269908 | GEO
Project description:Microglia are yolk sac-derived macrophages residing in the parenchyma of brain and spinal cord, where they interact with neurons and other glial cells by constantly probing their surroundings with dynamic extensions. 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.
2018-11-21 | GSE122768 | GEO
Project description:Microglia arise from yolk sac (YS) progenitors and are thought to persist throughout life with minimal input from adult hematopoiesis. However, whether brain-engrafted monocyte-derived macrophages (MDM) exist at homeostasis and during turnover, and how they function relative to yolk sac-derived microglia (YSM) remain unsettled. Here, we combine lineage tracing, pharmacological microglia depletion, and multi-omics profiling to define the ontogeny, identity, and function of MDM in the mouse brain. Despite sharing the parenchymal milieu, MDM display unique transcriptional and epigenetic landscapes distinct from YSM. Fate-mapping reveals that newly engrafted MDM transiently express CD206, echoing a developmental stage of embryonic microglial precursors. The engraftment and polarization of MDM are modulated by the CSF1R ligand IL 34 and the chemokine receptor CCR2. Furthermore, parabiosis and skull‑flap transplantation reveal that both blood and skull marrow supply the niche via distinct routes, yielding origin‑biased MDM states. Functionally, engraftment of MDM exacerbates cuprizone-mediated demyelination. Together, our study reveals the cellular dynamics of brain parenchymal macrophages at homeostasis and during turnover. We define the core molecular features and heterogeneous origins of MDM and imply their context-dependent roles in CNS pathology.
2026-03-11 | GSE313388 | GEO
Project description:Microglia arise from yolk sac (YS) progenitors and are thought to persist throughout life with minimal input from adult hematopoiesis. However, whether brain-engrafted monocyte-derived macrophages (MDM) exist at homeostasis and during turnover, and how they function relative to yolk sac-derived microglia (YSM) remain unsettled. Here, we combine lineage tracing, pharmacological microglia depletion, and multi-omics profiling to define the ontogeny, identity, and function of MDM in the mouse brain. Despite sharing the parenchymal milieu, MDM display unique transcriptional and epigenetic landscapes distinct from YSM. Fate-mapping reveals that newly engrafted MDM transiently express CD206, echoing a developmental stage of embryonic microglial precursors. The engraftment and polarization of MDM are modulated by the CSF1R ligand IL 34 and the chemokine receptor CCR2. Furthermore, parabiosis and skull‑flap transplantation reveal that both blood and skull marrow supply the niche via distinct routes, yielding origin‑biased MDM states. Functionally, engraftment of MDM exacerbates cuprizone-mediated demyelination. Together, our study reveals the cellular dynamics of brain parenchymal macrophages at homeostasis and during turnover. We define the core molecular features and heterogeneous origins of MDM and imply their context-dependent roles in CNS pathology.
2026-03-11 | GSE313387 | GEO
Project description:Ms4a3-Cre: R26-TdTomato: Cx3cr1-gfp mice allow discrimination between YS-derivd and monocyte-derived macrophages in the brain parenchyma and leptomeninges by color. We used single cell RNAseq for RNA profiling to compare YS-derived micrglia, monocyte-derived microglia, YS-derived leptomeningeal macrophages, and monocyte-derived leptomeningeal macrophages.
2024-12-02 | GSE282946 | GEO
Project description:Microglia and border-associated macrophages (BAMs) are critical for brain health and their dysfunction is closely linked to disease. Replacing brain macrophages holds significant therapeutic promise, but remains challenging. Here, we demonstrate that monocytes can efficienty replace all brain macrophages. Monocytes readily replaced embryonal BAMs upon their depletion and engrafted as monocyte-derived microglia (Mo-Microglia) upon more sustained niche availability. Mo-Microglia expanded comparably to their embryonic counterparts and showed similar longevity. However, monocytes were unable to replicate the unique identity of embryonically-derived BAMs and microglia. Using humanized models, we found that human monocytes exhibited similar behavior, enabling us to identify putative Mo-Microglia in Alzheimer’s disease patients. In mice and humans, the ontogeny of monocytes shaped their identity as brain macrophages. Importantly, mouse fetal liver monocytes exhibited a distinct epigenetic landscape and could develop a bonafide microglial identity. Our results illuminate brain macrophage development and highlight the potential of monocytes as an abundant progenitor source for brain macrophage replacement therapies.
2025-04-22 | GSE292830 | GEO