Mechanobiological Specialization of Choroid Plexus Macrophages Defined by Titin Expression
Bhatta, S.; Grzybowski, A.; Ortiz, G.; DiStasio, M.
Show abstract
Functioning both as the site of cerebrospinal fluid production and as an interface between the peripheral circulation and the central nervous system, the choroid plexus (ChP) modulates the gating of immune cells and signals from the periphery as they pass from the blood into cerebrospinal fluid. We generated a single-nucleus and spatial transcriptomic atlas of the adult human ChP, in donors with and without Alzheimers disease (AD), revealing transcriptionally and spatially distinct macrophage states. We identified a previously unrecognized population of titin-expressing (TTN+) tissue-resident macrophages characterized by coordinated activation of cytoskeletal remodeling, phagocytosis, autophagy, and inflammatory programs. Isoform-specific qPCR, protein immunofluorescence, and single-molecule FISH validated TTN expression in situ. In AD, TTN+ macrophages expand and undergo broad transcriptional rewiring, including activation of MEF2-linked mechanotransduction pathways, elevated senescence signatures, and a loss of ligand-receptor connectivity with epithelial, endothelial, and stromal partners. Collectively, our findings define a mechanosensitive macrophage program at the blood-CSF interface and uncover a TTN-associated shift in macrophage function and microenvironment integration in AD.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer's disease 97%
- Spatiotemporal analysis of gene expression in the human dentate gyrus reveals age-associated changes in cellular maturation and neuroinflammation 97%
- Applying high-resolution spatial transcriptomics to characterise the amyloid plaque cell niche in Alzheimer's Disease 96%
Similar papers in this journal
- Nerve-associated macrophages control adipose homeostasis across lifespan and restrain age-related inflammation 96%
- Activation of innate immune cGAS-STING pathway contributes to Alzheimer pathogenesis in 5xFAD mice 96%
- Quantitative phosphoproteomics uncovers dysregulated kinase networks in Alzheimer's disease 95%
Similar papers in this journal
Similar papers in this journal
- Knockout of the longevity gene Klotho perturbs aging- and Alzheimer's disease-linked brain microRNAs and tRNA fragments 97%
- Three-dimensional spatial transcriptomics uncovers cell type dynamics in the rheumatoid arthritis synovium 95%
- Hyperactive somatostatin interneurons near amyloid plaque and cell-type-specific firing deficits in a mouse model of Alzheimer's disease 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.