Biology subjects

Abadie, K.

Publications and source records attributed to Abadie, K..

3 recordsLinked to original sources

bioRxiv2026

SpatialTRACE predicts anatomical axes and regions in spatial transcriptomics and microscopy

Spatial transcriptomics measures gene expression in tissue sections. However, interpretation requires anatomical maps that link gene expression and cellular composition to tissue structure. Annotating entire sections often requires extensive manual labor. We developed SpatialTRACE (Tissue Region and Axis Coordinate Estimation), consisting of graph- and image-based models, to extend annotations of a few structures into tissue-wide maps of anatomical axes and regions. SpatialTRACE-Graph combines gene-expression profiles with spatial neighborhoods to predict anatomical coordinates or region membership throughout spatial transcriptomic datasets. In held-out mouse small-intestine sections, it predicted crypt-villus and epithelial-distance axis coordinates using as few as 10 annotated training villi and identified Peyer's patches from region annotations. SpatialTRACE-Image predicts the same anatomical axis coordinates and regions across entire tissue images from DAPI alone. This multiscale vision transformer learns from coordinate and region predictions generated by SpatialTRACE-Graph. We applied SpatialTRACE-Image to immunofluorescence images to map the anatomical distribution of antigen-specific P14 CD8 T cells responding to acute systemic infection with lymphocytic choriomeningitis virus (LCMV) Armstrong in the small intestine. Compared with the vehicle-treated section, a section treated with a retinoic acid receptor inhibitor contained fewer P14 CD8 T cells overall, with a smaller fraction in the upper-villus lamina propria and a relative enrichment in the muscularis. Overall, the SpatialTRACE models reduce repeated manual annotation and provide a route to extend anatomical maps learned from spatial transcriptomics to DAPI-containing microscopy data.

bioinformatics↗

bioRxiv2025

Tertiary lymphoid structures support the development of allergen-specific progenitor CD4+ T cells

Tissue-resident memory CD4+ T cells (TRM) are key sentinels of the adaptive immune response that provide a rapid, robust inflammatory response upon reactivation in non-lymphoid tissues. While CD4+ TRM are highly protective during reinfections or tumor growth, they are also critical mediators of autoimmunity and allergic disease. Using transcriptional analysis and flow cytometry we profiled the heterogeneity of allergen-specific CD4+ TRM in the lungs following house dust mite exposure and observe two distinct populations of cells: a proinflammatory Th2 lineage and a progenitor TCF1+ lineage that can repopulate the Th2 branch. Confocal microscopy revealed that these two subsets occupied distinct anatomical niches in the inflamed lungs, with Th2 cells localized to the airways while TCF1+ cells localized within pulmonary tertiary lymphoid structures (TLS). Spatial transcriptomics affirmed the TLS as a tissue progenitor niche and highlight the transcriptional progression from progenitor to Th2 cell reflected in the TLS:airway axis. Manipulations to promote or ablate TLS development resulted in increased or decreased TCF1 expression among allergen-specific T cells, respectively. Finally, we identify the PD1 pathway as a critical signal localized to the TLS core and demonstrate that TCF1+ cells in the TLS are responsive to anti-PD1 treatment. Together, these data shape our understanding of tissue CD4+ T cell responses across space and time and highlight TLS as a critical therapeutic target that promotes the propagation of chronic inflammatory diseases.

immunology↗

bioRxiv2022

Flexible and scalable control of T cell memory by a reversible epigenetic switch

The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cell populations formed in response. This encoding emerges from the decisions of lymphocytes to maintain or lose self-renewal and memory potential during a challenge. By tracking responding CD8 T cells at the single-cell and clonal lineage level using time-resolved transcriptomics and quantitative live imaging, we identify a remarkably flexible decision-making strategy, whereby T cells initially choose whether to maintain or lose memory potential early after antigen recognition, but following pathogen clearance may regain memory potential if initially lost. Mechanistically, this flexibility is implemented by a cis-epigenetic switch that silences the memory regulator TCF1 in a stochastic and reversible manner in response to stimulatory inputs. Mathematical modeling shows how this strategy allows memory T cell numbers to scale robustly with pathogen virulence and immune response magnitudes. We propose that flexibility and stochasticity in cellular decision making ensures optimal immune responses against diverse threats.

immunology↗