# RNA2seg: a generalist model for cell segmentation in image-based spatial transcriptomics

**Authors:** Thomas Defard, Alice Blondel, Sebastien Bellow, Anthony Coleon, Guilherme Dias de Melo, Florian Mueller, Thomas Walter

PMC · DOI: 10.1186/s13059-025-03908-9 · Genome Biology · 2026-01-30

## TL;DR

RNA2seg is a new cell segmentation tool for spatial transcriptomics that improves accuracy by using RNA data and cell stains.

## Contribution

RNA2seg introduces a generalist segmentation model trained on diverse datasets using a teacher-student approach.

## Key findings

- RNA2seg shows superior performance in cell segmentation using RNA point clouds and stainings.
- The model performs well in zero-shot and few-shot settings.
- It was trained on over 4 million cells from MERFISH and CosMx datasets across seven organs.

## Abstract

Imaging-based spatial transcriptomics enables high-resolution spatial mapping of RNA species. A key challenge in imaging-based spatial transcriptomics is accurate cell segmentation to assign each RNA molecule to the right cell. Here, we present RNA2seg, a novel segmentation algorithm trained on over 4 million cells from MERFISH and CosMx datasets across seven organs using a teacher-student training scheme. RNA2seg integrates RNA point clouds and all available membrane and nuclear stainings. Validation on manually annotated data shows superior performance including in zero-shot and few-shot settings.

The online version contains supplementary material available at 10.1186/s13059-025-03908-9.

## Full-text entities

- **Diseases:** IST (MESH:C564543), ST (MESH:D008569), melanoma (MESH:D008545)
- **Chemicals:** ComSeg (-), DAPI (MESH:C007293), Poly-T (MESH:D011071)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Cricetus cricetus (black-bellied hamster, species) [taxon 10034]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12934110/full.md

## References

3 references — full list in the complete paper: https://tomesphere.com/paper/PMC12934110/full.md

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Source: https://tomesphere.com/paper/PMC12934110