Cheung, K. P. | Search bioRxiv

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↗

bioRxiv2022

Growth limitation via chemically complex carbohydrates reduces sensitivity of synthetic human gut communities to perturbations

Dietary fiber affects the composition and functions of microbial communities that reside in the human gut. However, we lack a detailed and quantitative understanding of how these nutrients shape microbial community dynamics, interaction networks and systems-level properties. Using synthetic human gut communities coupled to computational modeling, we dissect the effects of varied fiber types or their constituent sugars on community assembly and sensitivity to perturbations. By quantifying carbohydrate chemical complexity, we demonstrate that microbial growth decreases as a function of complexity. We further demonstrate that the balance of species occupying distinct metabolic niches is altered by the presence of chemically complex carbohydrates. The frequency of negative inter-species interactions is reduced in the presence of complex carbohydrates. Communities grown in complex carbohydrates reproducibly assemble from a wide range of initial species abundances and display reduced sensitivity to invasion. Resource competition is identified as a key mechanism influencing the response of communities to perturbations. The strength of resource competition can promote sensitivity of community assembly to variations in initial species proportions and impact community resistance to invasion. By limiting microbial growth, complex carbohydrates promote the expansion of species occupying niches beyond carbohydrate utilization, shape the distribution of inter-species interactions, which in turn determines the communitys response to perturbations.

ecology↗