Biology subjects

Casey, O.

Publications and source records attributed to Casey, O..

4 recordsLinked to original sources

bioRxiv2026

The CD8 immgenT framework as a universal reference of mouse CD8 Tαβ cell differentiation states

Mouse CD8+ T cell differentiation has been studied extensively in models of infections and tumors, yet no unified framework spans the full spectrum of immunological contexts. Within the immgenT project, we profiled RNA, surface markers, and TCR clonotypes in conventional CD8+ T cells across >600 samples, spanning multiple perturbations, tissues, and timepoints. Twenty-one clusters across naive, effector, circulating memory, tissue-resident memory, progenitor-exhausted, and terminally-exhausted CD8+ T cell compartments emerged, with striking molecular convergence across acute and chronic infections, tumors, autoimmunity, aging, and homeostasis, illustrating that shared transcriptional states support protective or dysfunctional outcomes depending on developmental history and microenvironment. We validate immgenT as a comprehensive reference by integrating external datasets from conditions not represented in immgenT and by defining a flow cytometry panel spanning the CD8+ T cell landscape. Thus, immgenT-CD8 provides a molecular framework for harmonizing CD8+ T cell literature and clarifies relationships across diverse immune challenges.

immunology↗

bioRxiv2026

immgenT Treg: A Reference Landscape of Regulatory T Cell States in Mice

CD4+FoxP3+ regulatory T cells (Tregs) are central to immunity, tolerance, and tissue homeostasis, yet their extensive heterogeneity lacks a unifying framework. Within the immgenT project, we profiled gene expression, surface markers and TCR clonotypes of mouse Tregs. Using a joint RNA-protein deep generative model, we define the Treg landscape, organized around eight conserved clusters shared across tissues and conditions, with immune context reshaping their relative abundance rather than generating new states, including a prominent circulating effector Treg population enriched in select non-lymphoid tissues. We validate this framework by integrating external datasets from conditions not represented in immgenT and by defining a flow cytometry panel spanning the Treg landscape. Together, immgenT provides a scalable, reusable reference that unifies Treg heterogeneity across tissues and immune challenges.

immunology↗

bioRxiv2026

immgenT: A Comprehensive Reference of Convergent T-cell States in the Mouse

The immgenT collaborative project generated a comprehensive molecular atlas of T cells spanning virtually all mouse organs and disease states, profiling ~800,000 cells from 750 samples with RNA, 128-plex surface protein, and {beta}TCR sequence. Applying a deep generative model to joint RNA and protein data defined the landscape of T-cell states organized into eight lineages and 107 robust clusters, integrating similar cells from different contexts, and resolving prior nomenclatures. Analysis of effector molecules, transcription factors and modules showed that both immunological functions and regulatory programs are shared across cell states. This framework provides a stable, reusable reference, demonstrated by computationally integrating 16 external datasets from diverse biological contexts. A set of public web tools supports browsing of these data and mapping of any dataset onto the immgenT framework. These results propose a molecular classification of T cells organized around a set of shared states reused across immunological contexts.

immunology↗

bioRxiv2026

The αβTCR repertoire at scale in the immgenT dataset

The immense T cell receptor (TCR) repertoire is shaped by VDJ combinatorial diversity, imprecise rearrangements, and clonal selection. The immgenT Project generated scRNA and TCRseq to map paired {beta}TCR repertoires across 734 mouse samples from diverse tissues and challenge conditions. Compositional analysis uncovered some extreme junctional architectures. Beyond probabilistic V and J pairing, over-represented joins suggested non-randomness in fine joining, broadening the precedent of quasi-invariant iNKT and MAIT TCRs. We charted public clonotypes linked to self or environmental antigens in the main lineages. Tissue analyses revealed compartmentalized tissue-specific expansions. Unproductive and productive rearrangements of a V gene appeared to interfere specifically with each other, at chromatin or RNA levels. Unexpectedly, allelic exclusion at TCR{beta} proved less stringent than thought, and we identified rearrangements of TCR in immature pre-T stages. This organism-wide look into the TCR repertoire offers novel insights on the evolutionary and immunological pressures on TCR repertoire selection.

immunology↗