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Sarah A Teichmann

Publications and source records attributed to Sarah A Teichmann.

5 recordsLinked to original sources
PubMed2026

An integrated single-cell and spatial proteotranscriptomics atlas of fibroblast-driven immunoregulation within the human adult oral cavity.

The immunoregulatory architecture of human oral tissues remains poorly defined. We present an integrated single-cell and spatial proteotranscriptomic atlas profiling >250,000 single-cell transcriptomes and >4 million spatially resolved cells across 13 niches. Using our AI-enabled AstroSuite, we defined neighborhoods and interaction modules, revealing peri-epithelial fibroblast-centered hubs enriched in effector cytokines. We harmonized fibroblast subtypes (universal, immune, peri-epithelial, peri-vascular, peri-neural, antigen-presenting cell [APC]-like, stress responsive, and myofibroblasts) with stress-responsive subtypes partitioning between mucosae and glands (type I and II). Spatial multiomics mapped ligand-receptor programs and identified mucosal stress-responsive fibroblasts as putative immunoregulatory hubs. Niche-aware integration of healthy and diseased datasets revealed fibroblast rewiring into inflammatory and reparative niches. Disease neighborhoods exhibited expansion of major histocompatibility complex (MHC)-I+, MHC-II+, and programmed cell death ligand 1 (PD-L1)+ fibroblasts and predicted spatial engagement with T cells at tertiary lymphoid structures. Together, this atlas identifies fibroblasts as central regulators of structural immunity and provides a scalable framework to target stromal-immune interactions across barrier organs.

Journal Article↗
PubMed2025

GZMK+CD8+ T cells target a specific acinar cell type in Sjögren's disease.

OBJECTIVES: Sjögren's disease (SjD) is a systemic autoimmune disorder characterized by dysfunction of exocrine glands, particularly the salivary and lacrimal glands, with no clear etiology or effective therapy. This study explores the complex interplay of varied cell types in the salivary glands and their role in the pathology of Sjögren's disease. METHODS: Utilizing single-cell and spatial transcriptomics alongside spatial immunophenotyping to analyze human minor salivary glands, we developed a comprehensive understanding of the cellular landscape of non-SjD salivary glands and how that landscape changes in SjD patients. In vitro cellular assays and novel patient-derived primary epithelial cells were co-cultured with autologous T cells to confirm effector states and the delivery and effect of disease-associated granzymes. RESULTS: We identified previously unrecognized heterogeneity among acinar cells, including a PRR4⁺CST3⁺WFDC2⁻ seromucous acinar population that is selectively lost in Sjögren's disease. Expression and organizational changes were linked to clinical features: (i) T cells in the glands of SSA⁺, high-focus score patients showed increased transcriptional signatures of activation, antigen presentation, and apoptosis resistance compared with patients with mild or moderate disease, and (ii) patients with low immune infiltration exhibited distinct epithelial organization. Notably, GZMK⁺CD8⁺ T cells, which accumulate with disease severity, displayed a cytotoxic transcriptional program, degranulated upon stimulation ex vivo, and localized spatially with immune-engaged epithelial cells. Functional assays demonstrated that GZMK activates interferon signaling in vitro, and autologous co-cultures of patient-derived T cells and epithelial cells validated these findings. CONCLUSIONS: Using single-cell and spatial transcriptomics and proteomics, this study identifies a selective loss of PRR4⁺CST3⁺WFDC2⁻ seromucous acinar cells and a rise in GZMK⁺CD8⁺ T cells in Sjögren's disease, revealing distinct immune-mediated epithelial remodeling and interferon-driven dysfunction across diverse clinical presentations. These findings uncover a novel sub-cytolytic effector mechanism by which GZMK⁺CD8⁺ T cells impair mitochondrial integrity and activate innate immune signaling, linking epithelial injury to type I interferon responses and offering new therapeutic targets.

Humans↗
PubMed2025

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age.

The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood and lymphoid and mucosal tissues from 24 organ donors aged 20-75 years. We annotated major lineages (T cells, B cells, innate lymphoid cells and myeloid cells) and corresponding subsets using a multimodal classifier and probabilistic modeling for comparison across tissue sites and age. We identified dominant site-specific effects on immune cell composition and function across lineages; age-associated effects were manifested by site and lineage for macrophages in mucosal sites, B cells in lymphoid organs, and circulating T cells and natural killer cells across blood and tissues. Our results reveal tissue-specific signatures of immune homeostasis throughout the body, from which to define immune pathologies across the human lifespan.

Humans↗
PubMed2025

Integrated histopathology, spatial and single cell transcriptomics resolve cellular drivers of early and late alveolar damage in COVID-19.

The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding of the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data of COVID-19 and donor lung tissue with spatial transcriptomic data stratifying histopathological stages of diffuse alveolar damage. We identify changes in cellular composition across progressive damage, including waves of molecularly distinct macrophages and depletion of epithelial and endothelial populations. Predicted markers of pathological states identify immunoregulatory signatures, including IFN-alpha and metallothionein signatures in early damage, and fibrosis-related collagens in late damage. Furthermore, we predict a fibrinolytic shutdown via endothelial upregulation of SERPINE1/PAI-1. Cell-cell interaction analysis revealed macrophage-derived SPP1/osteopontin signalling as a key regulator during early steps of alveolar damage. These results provide a comprehensive, spatially resolved atlas of alveolar damage progression in COVID-19, highlighting the cellular mechanisms underlying pro-inflammatory and pro-fibrotic pathways in severe disease.

COVID-19↗
PubMed2023

Dandelion uses the single-cell adaptive immune receptor repertoire to explore lymphocyte developmental origins.

Assessment of single-cell gene expression (single-cell RNA sequencing) and adaptive immune receptor (AIR) sequencing (scVDJ-seq) has been invaluable in studying lymphocyte biology. Here we introduce Dandelion, a computational pipeline for scVDJ-seq analysis. It enables the application of standard V(D)J analysis workflows to single-cell datasets, delivering improved V(D)J contig annotation and the identification of nonproductive and partially spliced contigs. We devised a strategy to create an AIR feature space that can be used for both differential V(D)J usage analysis and pseudotime trajectory inference. The application of Dandelion improved the alignment of human thymic development trajectories of double-positive T cells to mature single-positive CD4/CD8 T cells, generating predictions of factors regulating lineage commitment. Dandelion analysis of other cell compartments provided insights into the origins of human B1 cells and ILC/NK cell development, illustrating the power of our approach. Dandelion is available at https://www.github.com/zktuong/dandelion .

Humans↗