ArticleGenome medicine2023
Single-cell RNA-seq reveals alterations in peripheral CX3CR1 and nonclassical monocytes in familial tauopathy.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Bone marrow myelopoiesis dysfunction in Alzheimer's disease limits monocyte homing to the brain and drives disease progression.Nature neuroscience · 2026Article
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- Circulating immune profiling reveals impaired monocyte states and trajectories driving immunosuppression in glioblastoma.Journal of neuroinflammation · 2026Article
- Genomic insights into the tunicamycin-induced endoplasmic reticulum stress response in peripheral blood mononuclear cells: A comprehensive RNA sequencing analysis.Biochemistry and biophysics reports · 2026Article
- Construction of a Computationally Inferred Single-Cell miRNA Activity Atlas and Analysis of Regulatory Networks in Spinal Cord Injury.Journal of molecular neuroscience : MN · 2026Article
- When imaging technology meets single-cell omics: new paradigm in developmental biology.Cell regeneration (London, England) · 2025Review
- Monocytes and cervical ripening: a narrative review of prolonged labor pathophysiology.Annals of medicine and surgery (2012) · 2025Review
- Review
- Single-cell RNA sequencing highlights the role of distinct natural killer subsets in sporadic amyotrophic lateral sclerosis.Journal of neuroinflammation · 2025Article
- CX3CL1 Regulation of Gliosis in Neuroinflammatory and Neuroprotective Processes.International journal of molecular sciences · 2025Review
- Peripheral proteinopathy in neurodegenerative diseases.Translational neurodegeneration · 2025Review
- Expansion of highly interferon-responsive T cells in early-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundEmerging evidence from mouse models is beginning to elucidate the brain's immune response to tau pathology, but little is known about the nature of this response in humans. In addition, it remains unclear to what extent tau pathology and the local inflammatory response within the brain influence the broader immune system.
methodsTo address these questions, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from carriers of pathogenic variants in MAPT, the gene encoding tau (n = 8), and healthy non-carrier controls (n = 8). Primary findings from our scRNA-seq analyses were confirmed and extended via flow cytometry, droplet digital (dd)PCR, and secondary analyses of publicly available transcriptomics datasets.
resultsAnalysis of ~ 181,000 individual PBMC transcriptomes demonstrated striking differential expression in monocytes and natural killer (NK) cells in MAPT pathogenic variant carriers. In particular, we observed a marked reduction in the expression of CX3CR1-the gene encoding the fractalkine receptor that is known to modulate tau pathology in mouse models-in monocytes and NK cells. We also observed a significant reduction in the abundance of nonclassical monocytes and dysregulated expression of nonclassical monocyte marker genes, including FCGR3A. Finally, we identified reductions in TMEM176A and TMEM176B, genes thought to be involved in the inflammatory response in human microglia but with unclear function in peripheral monocytes. We confirmed the reduction in nonclassical monocytes by flow cytometry and the differential expression of select biologically relevant genes dysregulated in our scRNA-seq data using ddPCR.
conclusionsOur results suggest that human peripheral immune cell expression and abundance are modulated by tau-associated pathophysiologic changes. CX3CR1 and nonclassical monocytes in particular will be a focus of future work exploring the role of these peripheral signals in additional tau-associated neurodegenerative diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.