Diversity and immune dynamics of choroid plexus macrophages are shaped by distinct developmental origins [CD45_TotalSeq_ICV_injection]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE295783 | GEO | 2025/12/22
REPOSITORIES: GEO
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Project description:The choroid plexus (ChP) forms a critical interface between the central nervous system and systemic circulation. Despite its importance, the identity and dynamics of resident macrophages remain incompletely understood. Using single-cell RNA sequencing, flow cytometry, lineage tracing, and imaging, we identified three biologically distinct macrophage populations in the homeostatic ChP, defined by expression of CD163, MHCII, or CD9. These subsets arise from different combinations of primitive and definitive hematopoietic waves, occupy distinct anatomical niches, and differentially rely on CSF1 and IL34 for survival. TGFβ signaling is required to maintain their phenotype, and deletion of Tgfbr2 in these cells induces phenotypic reprogramming and disrupts the ChP epithelial barrier. During neuroinflammation, ChP macrophages initiate IFN-I responses and secrete chemokines for CD8 T cell recruitment, while microglia mainly express chemokines for B cells. Finally, we identify phenotypically conserved macrophage subsets in the human ChP, suggesting evolutionary preservation of their phenotypic and functional features.
2025-12-22 | GSE295782 | GEO
Project description:The choroid plexus, responsible for cerebrospinal fluid production, is vital for brain functions. This organ serves as a crucial interface between the central nervous system and systemic circulation and thus faces constant immunological challenges. While resident macrophages within the choroid plexus provide immunosurveillance, their biological characteristics and immune dynamics remain poorly understood. In this study, we extensively examined the phenotype of choroid plexus macrophages using high-throughput single-cell RNA sequencing, flow cytometry, and imaging techniques. Our data unveiled three distinct macrophage populations within the homeostatic choroid plexus expressing either CD163, MHCII, or CD9. These macrophage subsets exhibited differential input from primitive and definitive hematopoietic waves, different spatial location and relied on distinct factors for survival. Upon neuroinflammation, these cells orchestrated IFN responses producing chemokines for effector CD8 T cells, while microglia predominantly expressed chemokines for B cells. Finally, we present evidence of phenotypically conserved macrophage subsets in the human choroid plexus.
2025-12-22 | GSE271590 | GEO
Project description:The choroid plexus, responsible for cerebrospinal fluid production, is vital for brain functions. This organ serves as a crucial interface between the central nervous system and systemic circulation and thus faces constant immunological challenges. While resident macrophages within the choroid plexus provide immunosurveillance, their biological characteristics and immune dynamics remain poorly understood. In this study, we extensively examined the phenotype of choroid plexus macrophages using high-throughput single-cell RNA sequencing, flow cytometry, and imaging techniques. Our data unveiled three distinct macrophage populations within the homeostatic choroid plexus expressing either CD163, MHCII, or CD9. These macrophage subsets exhibited differential input from primitive and definitive hematopoietic waves, different spatial location and relied on distinct factors for survival. Upon neuroinflammation, these cells orchestrated IFN responses producing chemokines for effector CD8 T cells, while microglia predominantly expressed chemokines for B cells. Finally, we present evidence of phenotypically conserved macrophage subsets in the human choroid plexus.
2025-12-22 | GSE271316 | GEO
Project description:The choroid plexus, responsible for cerebrospinal fluid production, is vital for brain functions. This organ serves as a crucial interface between the central nervous system and systemic circulation and thus faces constant immunological challenges. While resident macrophages within the choroid plexus provide immunosurveillance, their biological characteristics and immune dynamics remain poorly understood. In this study, we extensively examined the phenotype of choroid plexus macrophages using high-throughput single-cell RNA sequencing, flow cytometry, and imaging techniques. Our data unveiled three distinct macrophage populations within the homeostatic choroid plexus expressing either CD163, MHCII, or CD9. These macrophage subsets exhibited differential input from primitive and definitive hematopoietic waves, different spatial location and relied on distinct factors for survival. Upon neuroinflammation, these cells orchestrated IFN responses producing chemokines for effector CD8 T cells, while microglia predominantly expressed chemokines for B cells. Finally, we present evidence of phenotypically conserved macrophage subsets in the human choroid plexus.
2025-12-22 | GSE271592 | GEO
Project description:Biomaterials induce an immune response and mobilization of macrophages, yet identification and phenotypic characterization of functional macrophage subsets in vivo remain limited. We performed single-cell RNA sequencing analysis on macrophages sorted from either a biologic matrix [urinary bladder matrix (UBM)] or synthetic biomaterial [polycaprolactone (PCL)]. Implantation of UBM promotes tissue repair through generation of a tissue environment characterized by a T helper 2 (Th2)/interleukin (IL)–4 immune profile, whereas PCL induces a standard foreign body response characterized by Th17/IL-17 and fibrosis. Unbiased clustering and pseudotime analysis revealed distinct macrophage subsets responsible for antigen presentation, chemoattraction, and phagocytosis, as well as a small population with expression profiles of both dendritic cells and skeletal muscle after UBM implantation. In the PCL tissue environment, we identified a CD9 hi+ IL-36y + macrophage subset that expressed Th17-associated molecules. These macrophages were virtually absent in mice lacking the IL-17 receptor, suggesting that they might be involved in IL-17–dependent immune and autoimmune responses. Identification and comparison of the unique phenotypical and functional macrophage subsets in mouse and human tissue samples suggest broad relevance of the new classification. These distinct macrophage subsets demonstrate previously unrecognized myeloid phenotypes involved in different tissue responses and provide targets for potential therapeutic modulation in tissue repair and pathology.
2019-10-10 | GSE138027 | GEO
Project description:The choroid plexus (ChP) secretes a half-liter of cerebrospinal fluid (CSF) per day into the cerebral ventricular system and gates immune cell entry into the brain as the blood-CSF barrier. Acquired hydrocephalus, characterized by ventriculomegaly from CSF accumulation, is caused by both brain infection or hemorrhage and is treated by neurosurgical CSF diversion with attendant morbidity and long-term disability. We interrogated novel rat models of post-infectious (PIH) and post-hemorrhagic hydrocephalus (PHH) using a multi-omics, systems biology platform to elucidate mechanisms of disease. Integrated analysis of new genome-level transcriptomic and proteomic ChP datasets demonstrated that lipopolysaccharide in PIH, and blood breakdown products in PHH, trigger highly similar toll-like receptor-4 (TLR4)-dependent immune responses at the ChP-CSF interface. This includes the production of a CSF “cytokine storm” elicited from activated peripherally-derived and border-associated macrophages that accumulate at the ChP. Pro-inflammatory CSF signals stimulate their cognate receptors on ChP epithelial cells in paracrine manner to acutely increase CSF secretion rate via the TNF receptor associated SPAK kinase, which binds and activates a multi-ion transporter and channel complex at the ChP apical membrane. Genetic and pharmacological immunosuppression with repurposed drugs antagonizes SPAK-dependent CSF hypersecretion and prevents acute PIH and PHH. These data expand our understanding of ChP immune-epithelial cell crosstalk, reframe PIH and PHH as related inflammatory disorders vulnerable to systemic immunomodulation, and identify a druggable hub of ChP immune-secretory function that holds promise for other neurological disorders.
2023-02-20 | PXD030678 | Pride
Project description:Xenopus laevis juvenile frogs are uniquely capable of scarless skin regeneration, but the cellular and molecular mechanisms guiding this process remain incompletely understood. Macrophages are known as key regulators of wound healing, yet how their phenotypes shift over time and influence downstream regeneration in X. laevis has not been previously defined. It is well established that macrophage functions are imperative to mammalian wound healing. In vertebrate biology, macrophage polarization is dictated by two colony-stimulating factor-1 (CSF1) receptor ligands: CSF1 and interleukin-34 (IL34). While IL34 in mammals is critical to the development of epidermal macrophages known as Langerhans cells, the contribution of CSF1- and IL34-derived macrophages to skin wound repair remains unexplored. Pertinently, using the X. laevis model, previous work from our lab showed that CSF1- and IL34- macrophages are functionally distinct, formulating our hypothesis that these subsets play distinct roles during different phases of cutaneous wound repair. We therefore characterized full-thickness (epidermis and dermis) skin wounds in juvenile X. laevis during regeneration, analyzing transcript levels reflecting: M( infiltration (csf1r) and phenotype abundance (csf1 and il34), fibroblast activation (αSMA/acta2), and wound bed collagen composition (Picrosirius red staining). To assess the functional roles of macrophage phenotypes, we enriched wounds with recombinant X. laevis CSF1, IL34, or a vector control 3 days post-wounding (dpw) and analyzed wound responses at 7 and 14 dpw. Normal scarless regeneration in these juveniles demonstrated that macrophages transiently accumulated in the wound bed, peaking at 7–14 dpw. This coincided with elevated csf1 expression, which later declined as il34 levels rose. Fibroblast activation into myofibroblasts as well as collagen deposition followed this cytokine shift and restored collagen to pre-wound levels by 60 dpw. Subcutaneous IL34 enrichment at 3 dpw led to significantly increased αSMA expression at 7 and 14 dpw, a higher type I:III collagen ratio at 7 dpw, and suppression of inflammatory mediators coupled with enhancement of other, anti-inflammatory mediators at 7dpw. CSF1 enrichment had no significant effect on αSMA expression or subsequent collagen deposition, but did show a bias towards inflammatory mediators and the suppression of resolving and pro-reparative transcripts at 7 dpw. These findings suggest that early IL34 supplementation promotes a pro-regenerative macrophage phenotype that enhances myofibroblast activation and matrix remodeling while early CSF1 supplementation may contribute to prolonged inflammation and impaired tissue regeneration. Temporal modulation of macrophage-derived signals, particularly IL34, plays a critical role in directing scarless skin regeneration in X. laevis. These findings identify a conserved immunoregulatory axis with potential relevance to improving wound healing in non-regenerative species. Xenopus laevis juvenile frogs are uniquely capable of scarless skin regeneration, but the cellular and molecular mechanisms guiding this process remain incompletely understood. Macrophages are known as key regulators of wound healing, yet how their phenotypes shift over time and influence downstream regeneration in X. laevis has not been previously defined. It is well established that M( functions are imperative to mammalian wound healing. In vertebrate biology, M( polarization is dictated by two colony-stimulating factor-1 (CSF1) receptor ligands: CSF1 and interleukin-34 (IL34). While IL34 in mammals is critical to the development of epidermal M(s known as Langerhans cells, the contribution of CSF1- and IL34-derived macrophages to skin wound repair remains unexplored. Pertinently, using the X. laevis model, previous work from our lab showed that CSF1- and IL34- M(s are functionally distinct, formulating our hypothesis that these subsets play distinct roles during different phases of cutaneous wound repair. We therefore characterized full-thickness (epidermis and dermis) skin wounds in juvenile X. laevis during regeneration, analyzing transcript levels reflecting: macrophage infiltration (csf1r) and phenotype abundance (csf1 and il34), fibroblast activation (αSMA/acta2), and wound bed collagen composition (Picrosirius red staining). To assess the functional roles of macrophage phenotypes, we enriched wounds with recombinant X. laevis CSF1, IL34, or a vector control 3 days post-wounding (dpw) and analyzed wound responses at 7 and 14 dpw. Normal scarless regeneration in these juveniles demonstrated that macrophages transiently accumulated in the wound bed, peaking at 7–14 dpw. This coincided with elevated csf1 expression, which later declined as il34 levels rose. Fibroblast activation into myofibroblasts as well as collagen deposition followed this cytokine shift and restored collagen to pre-wound levels by 60 dpw. Subcutaneous IL34 enrichment at 3 dpw led to significantly increased αSMA expression at 7 and 14 dpw, a higher type I:III collagen ratio at 7 dpw, and suppression of inflammatory mediators coupled with enhancement of other, anti-inflammatory mediators at 7dpw. CSF1 enrichment had no significant effect on αSMA expression or subsequent collagen deposition, but did show a bias towards inflammatory mediators and the suppression of resolving and pro-reparative transcripts at 7 dpw. These findings suggest that early IL34 supplementation promotes a pro-regenerative M( phenotype that enhances myofibroblast activation and matrix remodeling while early CSF1 supplementation may contribute to prolonged inflammation and impaired tissue regeneration. Temporal modulation of macrophage-derived signals, particularly IL34, plays a critical role in directing scarless skin regeneration in X. laevis. These findings identify a conserved immunoregulatory axis with potential relevance to improving wound healing in non-regenerative species.
2025-10-22 | GSE306422 | GEO
Project description:DC, monocyte and macrophage networks are evolutionarily conserved but the distinct subsets have been difficult to distinguish due to shared overlapping phenotypic markers between the cells. Using transcriptome microarray profiling of human and mouse mononuclear phagocyte subsets, we have distinguished human dermal DCs from monocyte-derived cells and macrophages. Gene Expression from total RNA from human dermal macrophages, epidermal LCs and CD14+ cells subsets purified by FACS
2014-10-15 | E-GEOD-60317 | biostudies-arrayexpress
Project description:Macrophages are hematopoietic cells critical for innate immune defense, but also control organ homeostasis in a tissue-specific manner. Tissue-resident macrophages, therefore, provide a well-defined model to study the impact of ontogeny and microenvironment on chromatin state. Here, we profile the dynamics of four histone modifications across seven tissue-resident macrophage populations, as well as monocytes and neutrophils. We identify 12,743 macrophage-specific enhancers and establish that tissue-resident macrophages have distinct enhancer landscapes. Our work suggests that a combination of tissue and lineage-specific transcription factors form the regulatory networks controlling chromatin specification in tissue-resident macrophages. The environment has the capacity to alter the chromatin landscape of macrophages derived from transplanted adult bone marrow in vivo and even differentiated macrophages are reprogrammed when transferred into a new tissue. Altogether, these data provide a comprehensive view of macrophage regulation and highlight the importance of microenvironment along with pioneer factors in orchestrating macrophage identity and plasticity. 7 tissue-resident macrophage populations were isolated, as well as monocytes and neutrophils, and transcriptome analysis was performed. Experiment was done in duplicates.
2014-12-05 | E-GEOD-63340 | biostudies-arrayexpress
Project description:Structural and functional changes of the choroid plexus (ChP) have been reported in Alzheimer’s disease (AD). Nonetheless, the role of the ChP in the pathogenesis of AD remains largely unknown. We aim to unravel the relation between ChP functioning and core AD pathogenesis using a unique proteomic approach in mice and humans. We used an APP knock-in mouse model, APPNL-G-F, exhibiting amyloid pathology, to study the association between AD brain pathology and protein changes in mouse ChP tissue and CSF using liquid chromatography mass spectrometry. Mouse proteomes were investigated at the age of 7 weeks (n=5) and 40 weeks (n=5). Results were compared with existing human AD CSF proteomic data (n=496) to identify key proteins and pathways associated with ChP changes in AD.
2024-08-10 | PXD052590 | Pride