A Gene-Program Architecture of Mouse T cells
- 1Departments of Pathology, University of Chicago, Chicago, IL, USA
Abstract
We present immgenT-GP, a gene-program framework for resolving mouse T cell heterogeneity across the immgenT atlas. On ~ 800,000 T cells spanning lineages, organs, and immune challenges, we defined 200 reproducible gene programs, discovered by empirical Bayes matrix factorization approach and validated through a new deep learning approach, that capture major axes of T cell variation, including lineage identity, activation states and tissue location. Gene-program analysis complemented cluster-based annotation by decomposing T cell states into molecular modules, revealing quantitative, shared, modules not represented with discrete labels alone. Across tissues, gene programs reflected both tissue-imposed programs and changes in cluster composition. Integrating GP activity with cell-surface marker expression from the CITE-seq data, revealed that markers can report different programs depending on lineage and context. Together, immgenT-GP extends the atlas from a map of T cell states to a molecular reference of the programs that underlie them.
Related
- An inducible human LDLR transgenic mouse model for enhanced lentiviral gene delivery to murine immune cells
- Ductal myofibroblasts reactivate contractile program to stabilize alveolar architecture during lung regeneration
- Reusable modular architecture enables flexible cognitive operations in the mouse brain and artificial recurrent networks
- Stable large-scale network architecture and structured individual variability in the awake mouse brain
- Spatiotemporal Clonal Architecture of the Newborn Mouse Forebrain
BibTeX
@misc{zhang2026geneprogram,
title = {{A Gene-Program Architecture of Mouse T cells}},
author = {Z. Zhang and T. Wang and S. S. Panigrahi and P. Carbonetto and M. Stephens and C. Benoist and S. Mostafavi and M. Brbic and D. Zemmour and the immgenT Project},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.751918},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.751918v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - A Gene-Program Architecture of Mouse T cells
AU - Z. Zhang
AU - T. Wang
AU - S. S. Panigrahi
AU - P. Carbonetto
AU - M. Stephens
AU - C. Benoist
AU - S. Mostafavi
AU - M. Brbic
AU - D. Zemmour
AU - the immgenT Project
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.751918
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.751918v1
AB - We present immgenT-GP, a gene-program framework for resolving mouse T cell heterogeneity across the immgenT atlas. On ~ 800,000 T cells spanning lineages, organs, and immune challenges, we defined 200 reproducible gene programs, discovered by empirical Bayes matrix factorization approach and validated through a new deep learning approach, that capture major axes of T cell variation, including lineage identity, activation states and tissue location. Gene-program analysis complemented cluster-based annotation by decomposing T cell states into molecular modules, revealing quantitative, shared, modules not represented with discrete labels alone. Across tissues, gene programs reflected both tissue-imposed programs and changes in cluster composition. Integrating GP activity with cell-surface marker expression from the CITE-seq data, revealed that markers can report different programs depending on lineage and context. Together, immgenT-GP extends the atlas from a map of T cell states to a molecular reference of the programs that underlie them.
ER -