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Multiple-stress is defined as the simultaneous or sequential exposure of plants to multiple abiotic constraints, which triggers regulatory programs that differ fundamentally from single-stress responses. In potato ( L.), drought, salinity, heat, and cold severely impair tuber development, yet the molecular architecture underlying resilience to combined stress remains unclear. We hypothesized that multi-stress conditions activate an integrated regulatory network linking tuber induction with stress-responsive metabolic and redox pathways. RNA-seq profiling of microtuberization under combined osmotic, salinity, heat, and cold stress was performed. Differential expression analysis identified shared differentially expressed genes (DEGs). A subset of upregulated genes was used for protein-protein interaction (PPI) network construction. Comparative regulatory analyses were performed, and selected genes were validated by qPCR. Statistical analyses were conducted to assess differential expression and network enrichment. A total of 2,046 shared DEGs were identified, including 1,212 upregulated and 834 downregulated genes. A PPI network constructed from 1,475 unique upregulated genes revealed 317 highly interconnected components. Network analysis identified the StSP6A-FD tuberigen complex as a central regulatory hub integrating developmental signaling with phenylpropanoid metabolism, oxylipin biosynthesis, and redox regulation. Multiple components were associated with hydrogen sulfide (H₂S) signaling, suggesting redox-gasotransmitter integration. Comparative regulatory analysis revealed conservation of the ERF-NAC-MYB-bZIP transcription factor framework, along with expansion of stress-responsive modules. Collectively, these findings establish a mechanistic framework linking tuber induction with adaptive metabolic remodeling under multi-stress conditions.

Paclobutrazol (PBZ) is a triazole-type plant growth regulator that interferes with gibberellin (GAs) biosynthesis by blocking the oxidation step that converts ent-kaurene into ent-kaurenoic acid; however, the developmental mechanisms linking GAs restriction with storage organ enlargement remain poorly understood. In potato, PBZ induces compact growth while promoting microtubers (MTs) expansion, suggesting that GAs depletion triggers coordinated developmental reprogramming rather than simply suppressing elongation. Here, we evaluated the phenotypic, histological, and transcriptomic responses associated with PBZ-induced MTs development in Solanum tuberosum L. PBZ treatment, which increased MTs size, suppressed stolon growth, and enhanced starch accumulation, indicating a shift toward storage tissue development. Transcriptomic analysis identified broad PBZ-responsive changes, including enrichment of pathways related to metabolism, ribosome function, carbon metabolism, plant hormone signaling, and cell cycle regulation. Network analyses revealed ATH1-associated modules connected with receptor-like kinases, transcriptional regulators, mitotic regulators, replication-licensing factors and condensin components, supporting coordinated regulation among growth control, localized proliferation, asymmetric division, endoreduplication, and chromatin stability. These patterns were further supported by the absence of a detectable gibberellic acid (GA3) peak in PBZ-treated samples. These findings support a model in which PBZ-responsive signaling is associated with developmental reprogramming toward radial expansion and reinforcement of storage tissue, providing a regulatory mechanism by which growth repression is coupled to microtube enlargement in potato.