Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 30 min ago
Peer-reviewedCC BYCell

Whole-transcriptome-scale isoform-resolved spatial imaging of single cells in tissues

  • Limor Cohen1
  • Aaron R. Halpern1
  • Timothy R. Blosser1
  • Z. Phil Che1
  • Xingjie Pan1
  • Xiaowei Zhuang2
  1. 1Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Department of Physics, Harvard University, Cambridge, MA 02138, USA
  2. 2Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Department of Physics, Harvard University, Cambridge, MA 02138, USA. Electronic address: [email protected]
Open at sourceDOICite

Abstract

Cell and tissue functions arise from complex interactions among numerous genes, and a systematic understanding of these functions requires isoform-resolved transcriptomic analysis of single cells with high spatial resolution. Here, we introduce an in situ RNA amplification method and its integration with multiplexed error-robust fluorescence in situ hybridization (MERFISH) to detect short RNA sequences and enable whole-transcriptome-scale, isoform-resolved spatial transcriptomics of individual cells in intact tissues. Using this approach, we imaged ∼33,000 distinct RNAs-including ∼23,000 genes and ∼10,000 isoforms-in the mouse brain. Our data enabled systematic analyses of region- and cell-type-specific gene programs and ligand-receptor-based cell-cell communications. These data further revealed rich spatial diversity and cell-type specificity in isoform usage across numerous genes, as well as brain structures particularly rich in isoform specificity. We anticipate broad application of this method for characterizing the molecular and cellular basis of tissue functions, unlocking previously inaccessible discoveries in cell and organismal biology.

Related

  1. scTHREAD: a cell-resolved long-read transcriptome database with linked isoform, poly(A), junction, and allelic evidence
    Zhi-Can Fu, Yelian Yan, Chunchun Wu +12
    Nucleic Acids ResearchPeer-reviewedCC BY-NC 4.0Full textMolecular biology & gene regulationCrossref
  2. STRAND: a comprehensive subcellular-resolved spatial transcriptome RNA architecture and navigation database
    Zhaoxu Wu, Yuying Huo, Wenqian Xu +2
    Nucleic Acids ResearchPeer-reviewedCC BY-NC 4.0Full textMolecular biology & gene regulationCrossref
  3. Perplexity as a metric for isoform diversity in the human transcriptome
    Megan D. Schertzer, S H Park, Jiayu Su +3
    Genome biologyPeer-reviewedCC BY9 citedMolecular biology & gene regulationOpenAlex
  4. Single-cell transcriptome analysis of muscle and blood tissues from a patient with a rare homozygous ANO5 variant causing limb-girdle muscular dystrophy type R12
    Ming Chen, Ge Dong, Yue Wang +8
    Frontiers in geneticsPeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMCPMCEurope PMC
  5. 59 Charting the murine immune landscape: high-plex spatial profiling across diverse tissues
    Alyssa Hernandez, Danielle M Fails
    Journal for ImmunoTherapy of CancerPeer-reviewedCC BYFull textMolecular biology & gene regulationDOAJ

Cite

BibTeXRIS
BibTeX
@article{cohen2026wholetranscriptomescale,
  title = {{Whole-transcriptome-scale isoform-resolved spatial imaging of single cells in tissues}},
  author = {Limor Cohen and Aaron R. Halpern and Timothy R. Blosser and Z. Phil Che and Xingjie Pan and Xiaowei Zhuang},
  journal = {Cell},
  year = {2026},
  month = jul,
  doi = {10.1016/j.cell.2026.06.027},
  url = {https://doi.org/10.1016/j.cell.2026.06.027},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Whole-transcriptome-scale isoform-resolved spatial imaging of single cells in tissues
AU  - Limor Cohen
AU  - Aaron R. Halpern
AU  - Timothy R. Blosser
AU  - Z. Phil Che
AU  - Xingjie Pan
AU  - Xiaowei Zhuang
PY  - 2026
DA  - 2026/07/16
JO  - Cell
DO  - 10.1016/j.cell.2026.06.027
UR  - https://doi.org/10.1016/j.cell.2026.06.027
AB  - Cell and tissue functions arise from complex interactions among numerous genes, and a systematic understanding of these functions requires isoform-resolved transcriptomic analysis of single cells with high spatial resolution. Here, we introduce an in situ RNA amplification method and its integration with multiplexed error-robust fluorescence in situ hybridization (MERFISH) to detect short RNA sequences and enable whole-transcriptome-scale, isoform-resolved spatial transcriptomics of individual cells in intact tissues. Using this approach, we imaged ∼33,000 distinct RNAs-including ∼23,000 genes and ∼10,000 isoforms-in the mouse brain. Our data enabled systematic analyses of region- and cell-type-specific gene programs and ligand-receptor-based cell-cell communications. These data further revealed rich spatial diversity and cell-type specificity in isoform usage across numerous genes, as well as brain structures particularly rich in isoform specificity. We anticipate broad application of this method for characterizing the molecular and cellular basis of tissue functions, unlocking previously inaccessible discoveries in cell and organismal biology.
SN  - 0092-8674
SN  - 1097-4172
ER  -