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[Display omitted] • Global transcriptome analysis revealed key metabolites biosynthetic related genes. • Organ-specific transcription factors may mediate root metabolic processes. • Novel simple sequence repeats were identified. • Root accumulating resveratrol and emodin are correlated to the local activities of their biosynthetic genes. Polygonum cuspidatum is an important medicinal plant, which produces bioactive stilbenes and quinones, has been developed to be an important economic crop and cultivated in the Qinba mountain area, central China for years. Little is understood about its genetic characterization, which has impeded functional genomic studies of P. cuspidatum. In order to tackle genetic insights into the metabolic pathways of natural products, a comprehensive transcriptome analysis was conducted using Illumina sequencing amongst five major organs, namely roots, stems, leaves, flowers, and fruits in P. cuspidatum. As a result, 219,411 non-redundant transcripts and 159,545 functionally annotated unigenes were identified with mean lengths of 662 and 813 nucleotides, respectively. Organ-specific gene analysis unveiled that flowers presents the most abundance of unique transcripts (7,366), whereas the least does in roots (1,052). The gene expression profiles related to the metabolism of resveratrol and anthraquinone were investigated, and the contents of bioactive compounds in the different organs were determined, revealing that resveratrol and emodin were preferentially accumulated in the roots. In addition, our transcription factor analysis suggested that some bHLH- and MYB-TF family genes showed organ-enriched expression patterns and may mediate the metabolic processes. A total number of 25,404 simple sequence repeats were identified, which will benefit germplasm identification and discrimination of P. cuspidatum varieties. This study presents the assembly of a de novo transcriptome that will promote the investigation of the biosynthetic genes of natural products in P. cuspidatum , and enrich the genetic knowledge of this medical plant. [ABSTRACT FROM AUTHOR]