Spatial and single-nucleus transcriptomic profiling reveal polarity and intracellular responses to mitochondrial dysfunction
Abstract
Organelle retrograde signaling studies have exclusively relied on bulk tissues, obscuring cell-type specificity, spatial organization, and heterogeneity within cell types. Here, we use single-nucleus and spatial RNA sequencing to define the cellular and spatial architecture of mitochondrial stress signaling in Arabidopsis thaliana. Inhibition of the mitochondrial electron transport chain by antimycin A and myxothiazol rapidly redistributed nuclei among transcriptional states within epidermal, leaf pavement, and mesophyll lineages, revealing that mitochondrial dysfunction reshapes cell identity trajectories rather than eliciting a uniform response. Stress-associated clusters were already present at low frequency in untreated samples, but the numbers of cells increased following stress treatments, suggesting that stress increases the proportion of nuclei occupying pre-existing transcriptional states. Gene-level analyses revealed distinct temporal dynamics and variable cell-state penetrance of mitochondrial stress markers and identified broadly responsive genes absent from earlier marker sets. Spatial transcriptomics resolved tissue-scale responses, spanning from pan-tissue induction to cell-type- and cluster-restricted activation, and uncovered pronounced adaxial–abaxial polarity in gene expression. Cell identity and spatial inferences were supported by extensive experimental validation using a custom 465-probe 10× Xenium panel and 52 promoter-GFP reporter lines. Together, these data provide a high-resolution framework for organelle-to-nucleus signaling and a resource of cell-type markers and spatial maps to dissect mitochondrial stress signaling and its integration with developmental and environmental pathways.
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BibTeX
@article{zhu2026spatial,
title = {{Spatial and single-nucleus transcriptomic profiling reveal polarity and intracellular responses to mitochondrial dysfunction}},
author = {Yanqiao Zhu and Minxuan Li and Jiahao Li and Rijad Sarić and Feiran Han and Xinxin Zhou and Xiachao Wang and Yuhua Liu and Chi Zhang and Huixia Shou and Ghazanfar Abbas Khan and Mathew G Lewsey and James Whelan},
journal = {The Plant Cell},
year = {2026},
month = oct,
doi = {10.1093/plcell/koag308},
url = {https://doi.org/10.1093/plcell/koag308},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Spatial and single-nucleus transcriptomic profiling reveal polarity and intracellular responses to mitochondrial dysfunction
AU - Yanqiao Zhu
AU - Minxuan Li
AU - Jiahao Li
AU - Rijad Sarić
AU - Feiran Han
AU - Xinxin Zhou
AU - Xiachao Wang
AU - Yuhua Liu
AU - Chi Zhang
AU - Huixia Shou
AU - Ghazanfar Abbas Khan
AU - Mathew G Lewsey
AU - James Whelan
PY - 2026
DA - 2026/10/08
JO - The Plant Cell
DO - 10.1093/plcell/koag308
UR - https://doi.org/10.1093/plcell/koag308
AB - Organelle retrograde signaling studies have exclusively relied on bulk tissues, obscuring cell-type specificity, spatial organization, and heterogeneity within cell types. Here, we use single-nucleus and spatial RNA sequencing to define the cellular and spatial architecture of mitochondrial stress signaling in Arabidopsis thaliana. Inhibition of the mitochondrial electron transport chain by antimycin A and myxothiazol rapidly redistributed nuclei among transcriptional states within epidermal, leaf pavement, and mesophyll lineages, revealing that mitochondrial dysfunction reshapes cell identity trajectories rather than eliciting a uniform response. Stress-associated clusters were already present at low frequency in untreated samples, but the numbers of cells increased following stress treatments, suggesting that stress increases the proportion of nuclei occupying pre-existing transcriptional states. Gene-level analyses revealed distinct temporal dynamics and variable cell-state penetrance of mitochondrial stress markers and identified broadly responsive genes absent from earlier marker sets. Spatial transcriptomics resolved tissue-scale responses, spanning from pan-tissue induction to cell-type- and cluster-restricted activation, and uncovered pronounced adaxial–abaxial polarity in gene expression. Cell identity and spatial inferences were supported by extensive experimental validation using a custom 465-probe 10× Xenium panel and 52 promoter-GFP reporter lines. Together, these data provide a high-resolution framework for organelle-to-nucleus signaling and a resource of cell-type markers and spatial maps to dissect mitochondrial stress signaling and its integration with developmental and environmental pathways.
SN - 1040-4651
SN - 1532-298X
ER -