Hierarchical Regulatory Networks Reveal Conserved Drivers of Plant Drought Response at the Cell‐Type Level

Drought is a critical environmental challenge affecting plant growth and productivity. Understanding the regulatory networks governing drought response at the cellular level remains an open question. Here, a comprehensive multi-omics integration framework that combines transcriptomic, proteomic, epigenetic, and network-based analyses to delineate cell-type-specific regulatory networks involved in plant drought response is presented. By analyzing nearly 30 000 multi-omics data samples across species, unique insights are revealed into conserved drought responses and cell-type-specific regulatory dynamics, leveraging novel integrative analytical workflows. Notably, CIPK23 emerges as a conserved protein kinase mediating drought tolerance through interactions with CBL4, as validated by yeast two-hybrid and BiFC assays. Experimental validation in Arabidopsis thaliana and Vitis vinifera confirms the functional conservation of CIPK23, which enhances drought resistance in overexpression lines. In addition, the authors' causal network analysis pinpoints critical regulatory drivers such as NLP7 and CIPK23, providing insights into the molecular mechanisms of drought adaptation. These findings advance understanding of plant drought tolerance and offer potential targets for improving crop resilience across diverse species.