Madhav Mantri

All Publications

• Single-cell splice isoform usage reveals distinct axes of cellular identity and senescence. bioRxiv : the preprint server for biology Mantri, M., Detweiler, A. M., Lee, J., Kwon, J. H., Zhou, A., Tong, L., Jones, R. C., Neff, N. F., Quake, S. R. 2026

  Abstract

  Alternative splicing greatly expands the diversity of gene products encoded by the human genome. Single-cell transcriptomic atlases have characterized human cell types through gene-level expression, but short-read sequencing has limited the ability to resolve full-length isoforms and their functional consequences. Here, we present a cross-tissue single-cell long-read isoform atlas spanning 26 human tissues. We identify hundreds of thousands of novel isoforms along with their cell-type-specific usage, and discover that over one-third of expressed isoforms are absent from existing reference databases. We further demonstrate that isoform usage is a structured, measurable axis of cellular identity that is distinct from gene expression. Applying this framework to cellular senescence, we resolve p16INK4a and p14ARF transcripts from the CDKN2A locus in individual cells and uncover cell-type-dependent isoform remodeling associated with the p16INK4a senescence program. This isoform-resolved single-cell atlas offers a versatile framework to dissect the cellular logic of isoform regulation in senescence and beyond.

  View details for DOI 10.64898/2026.09.11.748700

  View details for PubMedID 42779730

  View details for PubMedCentralID PMC13596200

• Tabula Sapiens reveals the non-coding RNA landscape across 22 human organs and tissues. bioRxiv : the preprint server for biology Lee, J., Mantri, M., Murthy, K., Seeker, L. A., Crowley, G., Jones, R. C., Quake, S. R. 2026

  Abstract

  The biological significance of non-coding RNAs has been increasingly appreciated as their roles in various cellular processes are uncovered. However, single-cell transcriptomic profiling of human samples has focused primarily on protein-coding genes by targeting polyadenylated RNA transcripts, leaving the expression patterns of non-coding RNA underexplored. Here, we expand Tabula Sapiens to the non-coding transcriptome with single-cell and single-nucleus total RNA sequencing across 22 human organs and tissues. By simultaneously profiling both polyadenylated and non-polyadenylated transcripts, the resulting dataset enables joint analysis of the protein-coding and non-coding transcriptomes at single-cell and subcellular resolution. Using these data, we assessed the cell type specificity of non-coding genes and found that a greater proportion of non-coding genes are differentially expressed by single cell types compared to protein-coding genes. We then compared single-cell and single-nucleus data from the same samples to infer subcellular localization patterns, revealing cell type-dependent nuclear and cytoplasmic enrichment of specific non-coding RNAs. Next, we showed that tRNA repertoires are cell type-specific and that this specificity is not simply explained by differences in codon usage across cell types. Finally, we characterized dynamic expression patterns of non-coding RNAs across the cell cycle and senescence-associated cell states, identifying non-coding genes with putative roles in cell division and growth arrest. Our work establishes a resource for investigating the landscape of non-coding RNAs across a diverse set of human tissues and cell types.

  View details for DOI 10.64898/2026.03.23.713770

  View details for PubMedID 41929159

  View details for PubMedCentralID PMC13041822

• Spatial Mapping of the Adaptive Immune Receptor Repertoire in Lymph Nodes During Viral Infection 2278 Jiang, S., Mantri, M., Maymi, V., Leddon, S. A., Bhandari, S., Vollmers, C., Fowell, D. J., Flyak, A., Rudd, B. D., De Vlaminck, I. OXFORD UNIV PRESS. 2025

  View details for DOI 10.1093/jimmun/vkaf283.213

  View details for Web of Science ID 001627055700001