Spatial and Single-Nucleus Transcriptomic Profiling Reveal Polarity and Intracellular Responses to Mitochondrial Dysfunction

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ID: 331847
2026
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Abstract
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 10x 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.
Reference Key
openalex_W7221044311 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Yanqiao Zhu, Minxuan Li, Jia Hao Li, Rijad Sarić, Feiran Han, 周欣欣, Xiachao Wang, Yuhua Liu, Chi Zhang, Huixia Shou, Ghazanfar Abbas Khan, Mathew G. Lewsey, James Whelan
Journal The Plant cell
Year 2026
DOI
10.1093/plcell/koag308
URL
https://doi.org/10.1093/plcell/koag308
Keywords Keywords not found

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