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Mutation-resolved single-cell transcriptomics reveals enhanced β-amyloid clearance in TET2-mutant human monocytes
Xiao Yang, Sameen Fatima, Salvador Sampere-Birlanga, Akshay Ware, Mariana Shumliakivska, Lukas Zanders, Srisurekha Radhakrishnan, Guillermo Luxán, David John, Stefan Günther, Silvia Mas-Peiro, Stefanie Dimmeler, Andreas M. Zeiher, Wesley T. Abplanalp
Xiao Yang, Sameen Fatima, Salvador Sampere-Birlanga, Akshay Ware, Mariana Shumliakivska, Lukas Zanders, Srisurekha Radhakrishnan, Guillermo Luxán, David John, Stefan Günther, Silvia Mas-Peiro, Stefanie Dimmeler, Andreas M. Zeiher, Wesley T. Abplanalp
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Research Letter Aging Immunology Neuroscience

Mutation-resolved single-cell transcriptomics reveals enhanced β-amyloid clearance in TET2-mutant human monocytes

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Abstract

Authors

Xiao Yang, Sameen Fatima, Salvador Sampere-Birlanga, Akshay Ware, Mariana Shumliakivska, Lukas Zanders, Srisurekha Radhakrishnan, Guillermo Luxán, David John, Stefan Günther, Silvia Mas-Peiro, Stefanie Dimmeler, Andreas M. Zeiher, Wesley T. Abplanalp

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Figure 1

TET2-mutant carriers and cells exhibit enhanced phagocytic signatures in aged individuals.

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TET2-mutant carriers and cells exhibit enhanced phagocytic signatures in...
(A) UMAP of PBMCs from aged individuals with or without TET2-CHIP, showing major immune populations. (B) Phagocytosis module scores across immune cell types. (C) Phagocytosis module scores in monocytes from No-CHIP controls and TET2-mutant individuals. (D) Mutation-resolved single-cell RNA-seq identifying WT and TET2-mutant cells. (E) Phagocytosis module scores in WT versus TET2-mutant monocytes. (F and G) Representative flow cytometry plots and quantification of β-amyloid uptake in siTET2 and control monocytes. (H) Fluorescence microscopy of β-amyloid uptake in monocytes. Statistics: Wilcoxon rank-sum test (C and E); paired 2-tailed Student’s t test (G). Data are means ± SEM. *P < 0.05.

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