# Coordinated single-nucleus responses for quantitative disease resistance involve a calcium-associated switch in transcriptional noise

## TL;DR

This study shows how plants use coordinated changes in gene activity and calcium signals to resist fungal infection, revealing the role of cellular variability in immune responses.

## Contribution

The study identifies a calcium-associated switch in transcriptional noise as a novel mechanism in plant quantitative disease resistance.

## Key findings

- Transcriptional noise increases temporarily before defense genes are activated in infected cells.
- Calcium variations correlate with changes in transcriptional noise across space and time.
- Cellular heterogeneity contributes to the coordination of plant immune responses at the organ level.

## Abstract

Efficient plant immune response requires concerted reprogramming of cellular transcriptomes both globally and locally at the site of infection. Upon inoculation by the fungal pathogen Sclerotinia sclerotiorum, plants show quantitative disease resistance characterized by transcriptional reprogramming of numerous genes with small phenotypic effect.

To study transcriptional heterogeneity across cells during quantitative disease resistance, we combine end-point single-nucleus RNA-sequencing and time-course RNA-seq of mock-treated and S. sclerotiorum-inoculated Arabidopsis thaliana leaves. We observe heterogeneity of plant immune responses across cell types and in sub-populations of mesophyll cells, and reconstruct the sequence of immune responses activation over time. The quantification of gene expression heterogeneity reveals a transient increase in intrinsic transcriptional noise followed by the activation of key defense genes and the rise of extrinsic transcriptional noise in infected cells. Using the R-GECO1 cytoplasmic calcium reporter, we find that the intensity of calcium variations upon S. sclerotiorum inoculation coincides with variations to transcriptional noise in space and time.

These results provide evidence that stochastic cell–cell variability plays a key role in commitment to plant immunity and in the coordination of plant defense at the organ scale. Our study offers new insights into the mechanisms underlying plasticity and robustness of plant immune responses that can inform the design of strategies to reduce pathogen damage to crops in unstable environments.

The online version contains supplementary material available at 10.1186/s13059-025-03906-x.