Imaging-based spatial isoform transcriptomics resolves transcript diversity at cellular and subcellular resolution
- 1Université Côte d'Azur, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), CNRS UMR7275, Inserm U1323, Sophia-Antipolis, France
Abstract
Spatial transcriptomics has transformed our understanding of tissue organization, yet current high-throughput approaches remain largely confined to a gene-centric paradigm, precluding systematic characterization of spatially resolved transcript isoform diversity. Here, we introduce imaging-based spatial isoform transcriptomics (iSiT), a framework enabling simultaneous large-scale gene expression and targeted transcript isoform profiling on the commercial Xenium platform. iSiT resolves alternative splicing events that alter internal transcript structure at cellular and subcellular resolution using a single junction-specific probe per target. To facilitate broader adoption, we developed ProbeHarbour, an open-source toolkit for the design, characterization and management of isoform-specific probes. We demonstrate iSiT in the postnatal mouse brain by combining the Prime 5K gene-level panel with isoform-specific detection of 45 synaptogenesis-associated genes. By extending spatial transcriptomics beyond gene-level measurements, iSiT provides a scalable and readily accessible framework for investigating spatial isoform regulation in development and disease.
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BibTeX
@misc{mcandrew2026imagingbased,
title = {{Imaging-based spatial isoform transcriptomics resolves transcript diversity at cellular and subcellular resolution}},
author = {E. McAndrew and M. Fierville and M. Gautier-Isola and M. Pignol and M.-J. Arguel and H. Cadis and R. Barres and B. Mari and P. BARBRY and K. Lebrigand},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.22.753429},
url = {https://www.biorxiv.org/content/10.64898/2026.09.22.753429v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Imaging-based spatial isoform transcriptomics resolves transcript diversity at cellular and subcellular resolution
AU - E. McAndrew
AU - M. Fierville
AU - M. Gautier-Isola
AU - M. Pignol
AU - M.-J. Arguel
AU - H. Cadis
AU - R. Barres
AU - B. Mari
AU - P. BARBRY
AU - K. Lebrigand
PY - 2026
DA - 2026/09/22
PB - bioRxiv
DO - 10.64898/2026.09.22.753429
UR - https://www.biorxiv.org/content/10.64898/2026.09.22.753429v1
AB - Spatial transcriptomics has transformed our understanding of tissue organization, yet current high-throughput approaches remain largely confined to a gene-centric paradigm, precluding systematic characterization of spatially resolved transcript isoform diversity. Here, we introduce imaging-based spatial isoform transcriptomics (iSiT), a framework enabling simultaneous large-scale gene expression and targeted transcript isoform profiling on the commercial Xenium platform. iSiT resolves alternative splicing events that alter internal transcript structure at cellular and subcellular resolution using a single junction-specific probe per target. To facilitate broader adoption, we developed ProbeHarbour, an open-source toolkit for the design, characterization and management of isoform-specific probes. We demonstrate iSiT in the postnatal mouse brain by combining the Prime 5K gene-level panel with isoform-specific detection of 45 synaptogenesis-associated genes. By extending spatial transcriptomics beyond gene-level measurements, iSiT provides a scalable and readily accessible framework for investigating spatial isoform regulation in development and disease.
ER -