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Diversity and immune dynamics of choroid plexus macrophages are shaped by distinct developmental origins

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE271630 | GEO | 2025/12/22

REPOSITORIES: GEO

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Diversity and immune dynamics of choroid plexus macrophages are shaped by distinct developmental origins [CD45_TotalSeq_ICV_injection]

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.

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Diversity and immune dynamics of choroid plexus macrophages are shaped by distinct developmental origins [bulk RNA-seq]

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.

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Diversity and immune dynamics of choroid plexus macrophages are shaped by distinct developmental origins

Project description:Diversity and immune dynamics of choroid plexus macrophages are shaped by distinct developmental origins

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Diversity and immune dynamics of choroid plexus macrophages are shaped by distinct developmental origins [CD45_TotalSeq_ICV_injection]

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