Plant leaves, harvesting light energy and fixing CO 2 , are a major source of foods on the earth. Leaves undergo developmental and physiological shifts during their lifespan, ending with senescence and death. We characterized the key regulatory features of the leaf transcriptome during aging by analyzing total-and small-RNA transcriptomes throughout the lifespan of Arabidopsis (Arabidopsis thaliana) leaves at multidimensions, including age, RNA-type, and organelle. Intriguingly, senescing leaves showed more coordinated temporal changes in transcriptomes than growing leaves, with sophisticated regulatory networks comprising transcription factors and diverse small regulatory RNAs. The chloroplast transcriptome, but not the mitochondrial transcriptome, showed major changes during leaf aging, with a strongly shared expression pattern of nuclear transcripts encoding chloroplast-targeted proteins. Thus, unlike animal aging, leaf senescence proceeds with tight temporal and distinct interorganellar coordination of various transcriptomes that would be critical for the highly regulated degeneration and nutrient recycling contributing to plant fitness and productivity.Most organisms undergo age-dependent developmental changes during their lifespans. The timely decision of developmental changes during the lifespan is a critical evolutionary characteristic that maximizes fitness in a given ecological setting (Leopold, 1961;Fenner, 1998;Samach and Coupland, 2000). Plants use unique developmental strategies throughout their lifespans as opposed to animals. In plants, most organs are formed postnatally from sets of stem cells in the seed. In addition, plants are sessile and cope with encountering environments physiologically, rather than behaviorally. Thus, they have developed highly plastic and interactive developmental programs to incorporate environmental changes into their developmental decisions (Pigliucci, 1998;Sultan, 2000).The leaf is an organ that characterizes the fundamental aspects of plants. Leaves harvest light energy, fix CO 2 to produce carbohydrates, and, as primary producers in our ecosystem, serve as a major food source on the earth. Leaves undergo a series of developmental and physiological shifts during their lifespans. A leaf is initially formed as a leaf primordium derived from the stem cells at the shoot apical meristem and develops into a photosynthetic organ through biogenesis processes involving cell division, differentiation, and expansion (Tsukaya, 2013). In the later stages of their lifespans, leaves undergo organ-level senescence and eventually death. Organlevel senescence in plants involves postmitotic senescence and is a term used similarly as "aging" in animals. During the senescence stage, leaf cells undergo dramatic shifts in physiology from biogenesis to the sequential 1 This research was supported by the Institute for Basic Science (IBS-R013-D1 and IBS-R013-G1), the DGIST R&D Program (2014010043, 2015010004, 2015010011, 20150100012, and 15-01-HRLA-01), Basic Science Research Program (2010-0...

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Supplementary data are available at Bioinformatics online.

Single-cell transcriptomic profiles analysis has proposed new insights for understanding the behavior of human gastric cancer (GC). GC offers a unique model of intratumoral heterogeneity. However, the specific classes of cells involved in carcinogenetic passage, and the tumor microenvironment of stromal cells was poorly understood. We characterized the heterogeneous cell population of precancerous lesions and gastric cancer at the single-cell resolution by RNA sequencing. We identified 10 gastric cell subtypes and showed the intestinal and diffuse-type cancer were characterized by different cell population. We found that the intestinal and diffuse-type cancer cells have the differential metaplastic cell lineages: intestinal-type cancer cells differentiated along the intestinal metaplasia lineage while diffuse-type cancer cells resemble de novo pathway. We observed an enriched CCND1 mutation in premalignant disease state and discovered cancer-associated fibroblast cells harboring pro-stemness properties. In particular, tumor cells could be categorized into previously proposed molecular subtypes and harbored specific subtype of malignant cell with high expression level of epithelial-myofibroblast transition which was correlated with poor clinical prognosis. In addition to intratumoral heterogeneity, the analysis revealed different cellular lineages were responsible for potential carcinogenetic pathways. Single-cell transcriptomes analysis of gastric pre-cancerous lesions and cancer may provide insights for understanding GC cell behavior, suggesting potential targets for the diagnosis and treatment of GC.

Recently, MET exon 14 deletion (METex14del) has been postulated to be one potential mechanism for MET protein overexpression. We screened for the presence of METex14del transcript by multiplexed fusion transcript analysis using nCounter assay followed by confirmation with quantitative reverse transcription PCR with correlation to MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH). We extracted RNAs from 230 patients enrolled onto the prospective molecular profiling clinical trial (NEXT-1) (NCT02141152) between November 2013 and August 2014. Thirteen METex14del cases were identified including 3 gastric cancer, 4 colon cancer, 5 non-small cell lung cancer, and one adenocarcinoma of unknown primary. Of these 13 METex14del cases, 11 were MET IHC 3+ and 2 were 2+. Only one out of the 13 METex14del cases was MET amplified (MET/CEP ratio > 2.0). Growths of two (gastric, colon) METex14del+ patient tumor derived cell lines were profoundly inhibited by both MET tyrosine kinase inhibitors and a monoclonal antibody targeting MET. In conclusion, METex14del is a unique molecular aberration present in gastrointestinal (GI) malignancies corresponding with overexpression of MET protein but rarely with MET amplification. Substantial growth inhibition of METex14del+ patient tumor derived cell lines by several MET targeting drugs strongly suggests METex14del is a potential actionable driver mutation in GI malignancies.