Journal of Integrative Plant Biology

The establishment of aphid-plant interaction involves the secretion of a salivary MIF protein. Morphological analyses revealed that aphid MpMIF1 prevents plant cell death, protects organelles from stress, and may promote plant cellular recovery. Co-expression of aphid MpMIF1 and the cell death inducer Npp1 revealed that MpMIF1 modulates autophagy-related genes ATG7/BECLIN1, impair plant senescence regulator ATAF1 and regulate apoptosis-like via Caspase-3-like activity. This effect on multiple-cell death pathways helps to maintain cellular homeostasis during aphid infection. Investigations on DNA Damage Response (DDR) signaling pathways demonstrated that aphid MpMIF1 reduces {gamma}H2A.X phosphorylation, maintains activity of the DNA repair protein RAD51 and stabilizes cell cycle checkpoint expression WEE1 under genotoxic stress. Therefore, MpMIF1 actively participates to the maintenance of a functional DDR. Finally, we showed that aphid MpMIF1 physically interacts with SOG1, a functional analog of animal p53 and central regulator of DDR, cell cycle arrest and programmed cell death in plants. These findings establish MpMIF1 as a key regulator of plant cell death during aphid-plant interactions and highlight its potential as a biotechnological tool for protecting major crops against aphid infection.

Salt stress alters plant development, including the floral transition, but regulation of timing of flowering by salt is poorly understood at the molecular level. To identify genetic loci regulating the floral transition under high soil salinity, we performed a genome-wide association study (GWAS) in Arabidopsis thaliana and identified natural variation at the UGT74E1-UGT74E2-BT3 (UUB) locus that correlates with bolting time specifically in response to salt stress. Genetic analysis revealed BT3 as a novel repressor of the floral transition in control conditions. Similarly, the putative IBA glycosylases UGT74E1 & UGT74E2 delay the floral transition in control conditions. Furthermore, we identified that IBA homeostasis regulators TOB1 and ECH2/IBR10 play a key role in the floral transition, and that ECH2/IBR10 are required for the early flowering phenotype of the ugt74e1/ugt74e2 double mutant, indicating that UGT74E1 & UGT74E2 delay flowering by altering IBA homeostasis. A pangenome analysis of the UUB locus revealed variation in the occurrence of the DNA transposon SAUERKRAUT (SKRT). CRISPR-mediated SKRT deletion in Col-0 affected gene expression both within and outside the UUB locus and caused a salt-dependent delayed floral transition. The delayed bolting phenotype of the skrt-2 mutant also depends on ECH2/IBR10 function, indicating that SKRT accelerates the floral transition by altering IBA homeostasis. Finally, targeted demethylation of SKRT resulted in delayed floral transition under salt stress. Taken together, our data show a role for SKRT and its DNA methylation levels in the salt-dependent bolting time response in Arabidopsis, revealing a novel molecular mechanism to control flowering in adverse conditions.

The transition from hulled to free-threshing grain was a pivotal event in wheat domestication, enabling efficient harvesting and processing. Threshability in tetraploid wheat is controlled primarily by the Q locus and two Tenacious glume (Tg) loci on chromosomes 2A and 2B, yet the molecular basis of the major Tg1-B locus remains incompletely characterized. Here, we phenotyped a durum wheat x wild emmer wheat (WEW) recombinant inbred line (RIL) population across two field environments and performed QTL analysis for glume tenacity (TG), threshability ratio (THRR), and seed number per spike (SDNPS). A total of 19 significant QTLs were detected across six chromosomes. The largest-effect loci for both TG and THRR co-localized on chromosome 2B, with LOD scores up to 14.22 and phenotypic variance explained up to 31.2%, corresponding to the previously described Tg1-B locus. To validate this QTL, the donor RIL was backcrossed three times to Svevo to generate a near-isogenic line, NIL-65 (BC3F5), confirmed by whole-genome skim sequencing to carry a homozygous WEW introgression at Tg1-B. A segregating BC4F2 population derived from NIL-65 confirmed that plants homozygous for the dominant Tg1-B allele displayed significantly higher glume tenacity and intact glume morphology compared to tg1-B sister lines, which exhibited basal glume cracking characteristic of the free-threshing phenotype. Genotyping-by-sequencing delimited the causal interval to an approximately 11 Mb introgression on chromosome 2B. These results confirm the major role of Tg1-B in determining glume tenacity in tetraploid wheat, provide a validated near-isogenic germplasm resource, and lay the foundation for fine-mapping and functional characterization of the underlying gene(s).

Durable resistance to soil-borne pathogens remains elusive in cereals, partly because susceptibility (S) genes that facilitate root infection have not been identified in monocots. In the model legume Medicago truncatula, the SCAR/WAVE complex member MtAPI functions as a root S-gene for microbial invasion. Whether SCAR gene associated susceptibility function is conserved in monocots, and whether SCAR gene inactivation can enhance root resistance in cereals, remains unknown. Here, we identify and characterize three SCAR genes in barley: HvSCAR-A, HvSCAR-B, and HvSCAR-C. Cross-species complementation assays indicate that HvSCAR-B and HvSCAR-C are functionally similar to MtAPI. While hscar-b and hvscar-c single mutants exhibited no major growth defects, hvscar-a mutants showed strongly reduced seed production, and a hvscar-b/c double mutant displayed shorter root hairs. Notably, the hvscar-b/c double mutant exhibited increased resistance to the hemibiotrophic pathogen Phytophthora palmivora but greater colonization by the symbiotic arbuscular mycorrhizal fungus Funneliformis mosseae, underscoring a complex role in plant root - microbe interactions. Our findings reveal a conserved susceptibility function of SCAR genes in monocots and identify api monocot homologs as promising targets for engineering disease resistance in cereals. This study offers new insights into SCAR protein functional diversification and its potential for improving root health in crop plants.

Concerns over climate change have intensified the demand for stress resistant crops like hybrid wheatgrass (HWG; Elymus hoffmannii, StStStStHH), a perennial forage species known for its exceptional salt and drought tolerance. However, hexaploidy and high heterozygosity have complicated efforts to resolve its genomic structure and evolutionary history. Here, we present high-quality, haplotype-resolved, chromosome-level genome assemblies for HWG (CDC Saltking) and its putative progenitor, bluebunch wheatgrass (Pseudoroegneria spicata). By integrating PacBio HiFi and ultra-long Oxford Nanopore sequencing with Hi-C scaffolding, we assembled the 10.7 Gb HWG genome into 21 pseudochromosomes per haplotype. Our phylogenomic analysis redefines the origin of the H subgenome, positioning it as an intermediate between Old-World Hordeum marinum (sea barley) and Hordeum brevisubulatum. Notably, we identified significant chromosomal rearrangements, including a unique duplication on St chromosome 4. Transcriptome analysis across multiple tissues revealed a pronounced expression dominance of the H subgenome. This dominance was not associated with reduced LTR density, suggesting that selective pressures for rapid adaptation of the latest subgenome entrant may drive its dominance. Finally, using the f-branch statistic, population genomic analysis of 189 accessions representing eight Elymus and Pseudoroegneria species revealed extensive reticulate evolutionary relationships and identified P. spicata as a major, asymmetric genetic donor within the wheatgrass complex. These resources provide a foundational framework for future genomic research and genetic improvement in grasses and for the introgression of stress-tolerance traits into cereal crops such as wheat. Key MessagesDevelopment of world-first high-quality chromosomal-level haplotype-resolved genome assemblies of hexaploid HWG and diploid progenitor, Pseudoroegneria spicata, enabled the identification of the subgenome origins. This study resolved the evolutionary placement of the St genome and clarified the history of polyploidization and hybridization in HWG. Homeolog expression bias in the H subgenome likely reflects selective pressure favoring greater gene retention and upregulation of functionally important genes, thereby enhancing hybrid fitness. Population structure analysis distinctly differentiates P. spicata, E. repens, E. hoffmannii from other European Pseudoroegneria species. The findings reveal the complex patterns of interspecific gene flow and population dynamics within the Elymus and Pseudoroegneria species.

Flexible developmental programs enable plants to customize their organ size and cellular composition. In leaves of eudicots, the stomatal lineage produces two essential cell types, stomata and pavement cells, and plants can adjust the total numbers and ratios of these cell types in response to external cues. Central to this flexibility is the stomatal lineage-initiating transcription factor, SPEECHLESS (SPCH). Here we explore the mechanisms underlying SPCHs involvement in environmental response. Using multiplexed CRISPR/Cas9 editing of SlSPCH cis-regulatory sequences in tomato, we identified variants with altered stomatal development responses to drought, light and temperature cues. By creating and live-cell tracking translational reporters of SlSPCH and its paralogues SlMUTE and SlFAMA, we revealed the corresponding cellular events that lead to the environmental change-driven responses in stomatal production and leaf form. Plants bearing the novel reporters and SlSPCH variants are powerful resources for fundamental and applied studies of tomato resilience in response to climate change.

Poplar seed fibers cause environmental and health concerns, yet their developmental mechanisms remain poorly understood. Here, we constructed a high-resolution spatiotemporal transcriptomic atlas of female poplar capsules by integrating single-nucleus and spatial transcriptomics. We delineated the developmental trajectory of seed fibers, confirming their origin from placenta cells, and identified three functionally distinct fiber cell subtypes involved in initiation, metabolic support, and elongation. Weighted gene co-expression network analysis (WGCNA) identified several hub transcription factors, including PtoMYB, PtoHDT1, PtoEIF6 and PtoPDF2, that may serve as key regulators of fiber development. Our study provides a cellular-resolution framework for understanding trichome development in woody perennials and offers candidate targets for functional characterization toward breeding low-fluff poplar cultivars. HighlightsO_LIA spatiotemporal transcriptomic atlas of poplar capsule development is constructed at single-cell resolution C_LIO_LIFiber cells originate from placenta cells and comprise three functionally distinct subtypes C_LIO_LIProvides molecular targets for breeding low-fluff poplar cultivars to mitigate environmental pollution C_LI

Previously, the chitin receptor-interacting protein kinase LIK1 (LysM receptor kinase 1/CERK1-interacting kinase) was shown to play an important role in regulating chitin signaling and plant defense. A limited proteolysis proteomics study revealed several LIK1-derived peptides that showed differential abundance between ATP-treated and mock-treated Arabidopsis samples, suggesting a possible involvement of LIK1 in extracellular ATP (eATP) signaling. To explore this possibility, LIK1 mutants were obtained and examined for their response to ATP. The results showed that mutations in LIK1 significantly reduced the expression of eATP-responsive genes. In addition, LIK1 was found to interact with the eATP receptor P2K1 and to be phosphorylated by it. The LIK1 protein was localized to the plasma membrane and its gene expression appeared to be ubiquitous. Collectively, these findings indicate that LIK1 not only contributes to chitin signaling but also participates in eATP signaling, highlighting its potential role as a shared component in multiple signaling pathways to regulate plant responses to diverse internal and external cues.

DNA methylation plays a central role in the regulation of gene expression. In plants, methylation occurs in the CG, CHG and CHH contexts, via distinct DNA methyltransferases including MET1, CMT3 and the RNA-directed DNA Methylation (RdDM) pathway via DRM2. In interspecific hybrids, these epigenetic mechanisms are confronted to a mixed small RNA population and two subgenomes harbouring specific methylation patterns, therefore generating unique expression profiles. The aim of this work was to understand these regulations by analysing gene expression, DNA methylation and small RNAs in a Citrus hybrid resulting from the cross between C. reticulata (mandarin) and C. australasica (finger lime). Haplotype-resolved subgenomes assembly identified hundreds of allele-specifically expressed genes. Asymmetric reprogramming of methylation was observed, in particular an increase in CHH in C. australasica haplotype. Surprisingly, CHH methylation, usually associated with gene silencing, was correlated here with increased expression, but also 24nt small RNA populations at their promoter regions. Similar analyses of the parental lines and other citrus species suggest the correlation between CHH methylation-enriched promoter and high expression level is not due to the hybridization, but seem to be generally true for all citrus. These observations suggest that, in citrus fruit, RdDM could activate transcription. This work also provides a full pipeline to analyse the expression profiles and DNA methylation in complex hybrids, which could be crucial for anticipating varieties resistant to diseases and the current threats affecting citriculture such as the Huanglongbing disease.

Sacha inchi (Plukenetia volubilis L.) is an emerging woody oilseed crop prized for its high alpha-linolenic acid (ALA) content. Despite its nutritional and economic value, the lack of high-quality genomic resources has hindered genetic improvement and the elucidation of its unique polyunsaturated fatty acid and lipid biosynthetic pathways. In this study, we report a high-quality, chromosome-scale genome assembly of sacha inchi with a total length of 710.62 Mb, integrated from Illumina, PacBio, and chromosome conformation capture (Hi-C) technology. The genome harbors 37,570 protein-coding genes, and 379.86 Mb (53.45%) of repetitive sequences. Phylogenomic analysis reveals that sacha inchi diverged from its closest relative Ricinus communis, [~] approximately 36.2 million years ago. Comparative genomics indicates that sacha inchi experienced only ancient whole genome duplication events. To elucidate the mechanisms governing ALA biosynthesis and triacylglycerol (TAG) accumulation in sacha inchi seeds, we performed temporal transcriptome profiling across six seed development stages. Our findings demonstrate that high TAG content is primarily driven by the sustained expression of biosynthetic genes and low activity of degradation genes during mid-to-late seed development. Notably, while genes encoding stearoyl-ACP desaturases (SADs) maintain the precursor pool, the expression of genes encoding fatty-acid desaturase 2 (FAD2) and fatty-acid desaturase 3 (FAD3) is positively correlated with the final accumulation of C18:2 and C18:3 fatty acids. We also identified lncRNAs as potential epigenetic regulators of these key pathways. This high-quality genome provides a critical foundation for elucidating the molecular mechanisms of seed growth and development in sacha inchi.

Plant amino acids function as both pathogen nutrients and essential drivers of systemic immunity. The regulation of amino acid homeostasis through transporters is a essential for mounting a robust and coordinated immune response in plants during pathogen infection. Using systems biology and integrative network science, we investigated bacterial virulence in Arabidopsis. By comparing gene coexpression networks of effector-triggered susceptibility (ETS) and pattern-triggered immunity (PTI), we uncovered a plant amino acid-related processes specifically linked to ETS. Integrating time-series transcriptomics, protein-DNA interactions, and mathematical simulations, we identified ANAC046 as a transcriptional regulator of amino acid processes during ETS. Single-cell RNA-Seq revealed that amino acid transporters are primarily expressed in companion and mesophyll cells, while functional validation confirmed ANAC046s roles in promoting susceptibility. Further integration of transcriptome and interactome data showed that amino acid-related genes interact with key immune hub proteins. Network topology analysis enabled the characterization of seven additional genes involved in plant defense. To support community-wide research, we developed MIData, an open-access platform for pre-analyzed Arabidopsis networks. Together, our findings demonstrate the power of systems-level approaches in uncovering hierarchical regulatory mechanisms underlying plant susceptibility to bacterial pathogens.

Barley (Hordeum vulgare L.) is an important crop in the world and its seed dormancy is primarily controlled by a Mitogen-Activated Protein Kinase Kinase 3 (MKK3) gene. Although kinase activity of MKK3 and its roles in barley post-domestication have been widely studied, the pre-domestication evolution of MKK3 and the spread of nondormant alleles among global barley varieties remain largely unexplored. In this study, we analyzed MKK3 sequences in barley and its wild progenitor (H. spontaneum) and identified two polymorphic miniature inverted-repeat transposable elements (MITEs). Comparative analyses indicated that the insertions/excision of the MITEs predated the current estimates of barley domestication. Examination of the barley pangenomes coupled with droplet digital (dd) PCR revealed extensive copy number variation of MKK3 and suggested that transposons likely drove tandem amplification of the MKK3 gene on chromosome 5H. Additionally, approximately 1-Kb MKK3 sequences were found on chromosomes 1H and 6H. Further analysis indicated that these short MKK3 sequences were captured by a CACTA transposon that also contained fragments from four other expressed genes. The acquisition of MKK3 was estimated to be between 1.9-2.5 million years ago. Together, these findings illuminate the dynamic pre-domestication evolution of the MKK3 gene and suggest three independent origins of highly nondormant barley worldwide including a unique lineage predominant in Ethiopian germplasm. This study reveals the pivotal roles of transposons in MKK3 evolution and provide helpful information for understanding the complex history of MKK3 gene in barley and also for improving preharvest sprouting (PSH) tolerant varieties under distinct natural conditions.

Hundreds of proteins in the cell require iron (Fe) or Fe-containing cofactors to function. However, how Fe2+ or Fe3+ are specifically allocated to each of these proteins in plant cells remains largely unknown. It has been proposed that Fe metalation could be driven by specific interactions with Fe-shuttling proteins known as Fe-chaperones. Here, we present the first family of plant Fe2+-chaperones (ICHAPs) with orthologues in dicots and monocots. The role of these proteins in Fe distribution to Fe-dependent metabolic processes has been illustrated using symbiotic nitrogen fixation in Medicago truncatula root nodules. ICHAP1 is a soluble Fe2+-binding protein that interacts with plasma membrane Fe2+ transporter NRAMP1, but not with symbiosome Fe2+-transporters. ICHAP1 mutants present altered Fe distribution in cells and they cannot fix nitrogen. A second family member, ICHAP2 is required to target Fe2+ to symbiosomes, as it accepts Fe2+ from ICHAP1 and interacts with symbiosome Fe2+-importer VTL8, but not with NRAMP1. These results indicate a path for Fe2+ allocation from the plasma membrane to the symbiosome through specific protein-protein interactions and Fe2+ exchange from NRAMP1 to ICHAP1, to ICHAP2, and to VTL8.

Sesame (Sesamum indicum) is one of the earliest domesticated oilseed crops and is valued for antioxidant lignans that stabilize oil quality. However, the genomic and evolutionary history of the genus Sesamum, including the origin of its allotetraploid relative S. radiatum and the diversification of lignan metabolism, remains poorly understood owing to limited chromosome-scale genomic resources. Here we present chromosome-level genome assemblies for three wild Sesamum species, two Ceratotheca species and a Japanese sesame cultivar to reconstruct genome and karyotype evolution across the Sesamum-Ceratotheca complex. Comparative analyses show that the derived x=16 lineage originated from an ancestral x=13 karyotype through chromosome fission, fusion and translocation, whereas another x=13 lineage underwent extensive restructuring associated with retrotransposon expansion. Phylogenomics places Ceratotheca within the x=16 Sesamum clade and reveals that S. radiatum originated through hybridization involving a C. sesamoides-like ancestor. The antioxidative lignan gene CYP92B14 was reintroduced via the BB progenitor, linking hybridization with restoration of oil-stabilizing metabolism during sesame evolution.

Macroautophagy is a conserved intracellular catabolic process in eukaryotes that participates in chloroplast degradation, through the selective breakdown of chloroplast components. Selective autophagy of membrane-bound organelles typically requires receptors that bridge organelle membranes and pre-autophagosomal structures. Here we identify OEP24.1 as a new receptor in the selective chloroplast piecemeal autophagy, supporting the degradation of stromal proteins. We found that the {beta}-barrel protein OEP24.1 is located at the outer membrane of plastid envelopes and on bodies budding off plastids into the cytosol and containing stroma proteins. OEP24.1 interacts physically with ATG8 autophagy proteins in a UIM dependent manner. OEP24.1-GFP and RFP-ATG8 colocalize with in mobile autophagosome-like puncta in the cytosol and in autophagic bodies within the vacuole. Delivery of OEP24.1 to vacuole lumen is dependent on active autophagy. OEP24.1 controls carbon allocation at the whole plant level, carbon concentrations in flowering stems and xylem composition. These phenotypes can be explained by the role of OEP24.1 in metabolite diffusion across the chloroplast envelope, and by its involvement in the facilitation of chloroplast quality control through piecemeal autophagy.

Pepper (Capsicum annuum L.) is a recalcitrant species regarding shoot regeneration, a trait that serves as a major bottleneck for the application of genetic engineering tools. In this study, comparative genetic analysis between a rare high-regeneration cultivar and a common low-efficiency cultivar identified a single nucleotide polymorphism (SNP) in PHYTOCHROME A SIGNAL TRANSDUCTION 1 (CaPAT1) that determines shoot regeneration efficiency. The T478C SNP in the high-efficiency cultivar converts a stop codon into an Arg codon, leading to translational read-through into the neighboring gene and forming an intact GRAS domain. This SNP-mediated formation of full-length CaPAT1 is essential for its dimerization. Notably, the overexpression of CaPAT1T478C in multiple low-efficiency cultivars, including both hot and bell peppers, significantly improved both shoot regeneration and transformation efficiency in the transformed T0 generation. These findings demonstrate the pivotal role of CaPAT1 in enhancing shoot regeneration and provide a robust strategy to overcome recalcitrance in pepper.

The RETINOBLASTOMA-RELATED (RBR) protein in plants functions as a cell-cycle inhibitor, regulating cell numbers in developing organs and establishing cellular quiescence during growth. Although the role of RBR counterparts in animals also involves regulating cell size, this potential function remains unexplored in plants. We investigated transgenic Arabidopsis plants with altered RBR levels and observed corresponding changes in cell size from embryogenesis through organ development. In addition, stomatal meristemoid cells with reduced RBR levels divided beyond the size threshold, whereas elevated RBR levels increased their size. RBR stimulated terminal differentiation in the stomatal lineage by inducing MUTE and CYCLIN D5;1 expression, whereas reduced RBR levels maintained asymmetric divisions through high SPEECHLESS and CYCLIN D3;1 expression. Interestingly, the cell proliferation-dependent phosphorylation of RBR at the conserved 911Ser site positively correlated with RBR protein levels in the transgenic lines and aligned with the effect of RBR on cell size. This study discusses the potential link between RBRs control of cell proliferation and cell size, providing new insights into the coordinated regulation of plant development.

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are essential regulators of plant growth, development, and stress adaptation. In this study, we performed a comprehensive genome-wide identification of SNARE genes in cucumber (Cucumis sativus L.), uncovering 51 putative members designated as CsSNAREs. Phylogenetic analysis confirmed that these genes cluster into five major clades: Qa-CsSNARE (14), Qb-CsSNARE (9), Qc-CsSNARE (10), Qb+c-CsSNARE (3), and R-CsSNARE (15). Bioinformatic analysis of their promoter regions, coupled with expression profiling under diverse abiotic stress conditions, highlighted a heightened responsiveness within the Qa-CsSNARE subfamily. To validate this, we selected representative Qa-CsSNARE genes for quantitative real-time PCR analysis under drought and salt stress. Among these, CsSYP121 was notably induced by salt treatment. We subsequently generated transgenic cucumber lines overexpressing CsSYP121 and challenged them with salinity. Phenotypic assessment, combined with measurements of reactive oxygen species (ROS) accumulation and K+/Na+ ratios, demonstrated that CsSYP121 overexpression (OE) confers enhanced salt tolerance and boosts antioxidant capacity. We propose a model wherein CsSYP121 mitigates ROS-induced cellular damage under salt stress, potentially through promoting K+/Na+ homeostasis, thereby improving plant performance under saline conditions. Our findings identify CsSYP121 as a promising candidate gene for breeding salt-tolerant crops.

Plant survival and growth depend partly on the ability to manage energy resources in response to changing environmental conditions. SnRK1 plays a central role in this process by restricting growth under energy-limiting conditions while promoting stress adaptation and survival. When activated, SnRK1 triggers transcriptional reprogramming that prioritizes energy-producing pathways. A key mediator of this response is the transcription factor bZIP63, whose activity is regulated by SnRK1-dependent phosphorylation. Given its roles in energy homeostasis and its interaction with the circadian clock, bZIP63 influences growth and is therefore a candidate component of the Metabolic Daylength Measurement (MDLM) system, which integrates starch and sucrose metabolism with circadian timing and photosynthetic duration to regulate vegetative growth under contrasting photoperiods. We show that 39 bZIP63 direct targets regulated by SnRK1 correspond to a subset of short-day-induced genes associated with the MDLM system and are downregulated in a bZIP63 T-DNA mutant (bzip63-2) and/or in an RNAi-induced silencing line (RNAiWs_L9). Downregulation of these genes was more extensive in RNAiWs_L9 than in bzip63-2, possibly due to the unexplained silencing of BAM4, a {beta}-amylase that promotes starch degradation. Under short-day conditions, the frameshift mutant bzip63-5 (Col-0), bzip63-2 (Ws), and the bzip1-1/bzip53-1/bzip63-5 (Col-0) triple mutant, which disrupts bZIP63 heterodimerization partners, showed similar deregulation of a subset of these genes and comparable growth inhibition, whereas both growth and gene deregulation were more strongly affected in RNAiWs_L9. We further show in two partially complemented bzip63-2 lines that bZIP63 protein levels increase toward the end of the night and decline toward the end of the day, in synchrony with the diel oscillation of its transcript. Additional analyses of these lines, together with bzip63-2 line overexpressing bZIP63, suggest that the timing and amplitude of bZIP63 accumulation contribute to shaping the expression profiles of a subset of the 39 MDLM-associated genes. Together, these findings indicate that bZIP63 participates in a regulatory network linking SnRK1 signaling, photoperiod-changes, and growth within the MDLM system.

Single-cell expression quantitative trait loci (sc-eQTL) analyses are powerful in identifying context-specific susceptibility genes from genome-wide association studies (GWAS) loci. However, few studies have comprehensively investigated cells of lung cancer origin in non-European populations. Here, we built a lung sc-eQTL dataset from 129 Korean women never-smokers with epithelial cell enrichment. eQTL mapping identified 2,229 genes with an eQTL in 33 cell types, including East Asian-specific findings when compared to predominantly European datasets. Integration with single-cell chromatin accessibility data demonstrated an enrichment of cell-type specific eQTLs in cell-type matched candidate enhancers, while shared eQTLs were more frequently found near promoters. Colocalization and transcriptome-wide association study unveiled 36 susceptibility genes from 22 cell types in 22 lung cancer loci, including 10 loci not achieving genome-wide significance in prior GWAS. Around 47% of these genes were from cells of the alveoli, underscoring their importance, especially in lung adenocarcinoma (LUAD) susceptibility. Focusing on the trajectory of alveolar epithelial cell regeneration, we detected 785 cell-state-interacting QTLs, which overlapped with 28% (10) of the identified susceptibility genes. Finally, we experimentally validated East Asian-and alveolar type 2 cell-specific eQTL of TCF7L2 underlying East Asian LUAD locus, 10q25.2. Consistent with its role as a Wnt/{beta}-catenin effector, TCF7L2 displayed significant effect on lung adenocarcinoma cell growth. Our data highlighted context-specific susceptibility genes, especially from alveolar cells of lung, contributing to lung cancer etiology.