研究成果

Ectopic ATP synthase complex (eATP synthase), located on cancer cell surface, has been reported to possess catalytic activity that facilitates the generation of ATP in the extracellular environment to establish a suitable microenvironment and to be a potential target for cancer therapy. However, the mechanism of intracellular ATP synthase complex transport remains unclear. Using a combination of spatial proteomics, interaction proteomics, and transcriptomics analyses, we find ATP synthase complex is first assembled in the mitochondria and subsequently delivered to the cell surface along the microtubule via the interplay of dynamin-related protein 1 (DRP1) and kinesin family member 5B (KIF5B). We further demonstrate that the mitochondrial membrane fuses to the plasma membrane in turn to...

The study of multiple “omes,” such as the genome, transcriptome, proteome, and metabolome has become widespread in biomedical research. High-throughput techniques enable the rapid generation of high-dimensional multiomics data. This multiomics approach provides a more complete perspective to study biological systems compared with traditional methods. However, the quantitative analysis and integration of distinct types of high-dimensional omics data remain a challenge. Here, we provide an up-to-date and comprehensive review of the methods used for omics data quantification and integration. We first review the quantitative analysis of not only bulk but also single-cell transcriptomics data, as well as proteomics data. Current methods for reducing batch effects and integrating heterogeneous...

The study of multiple “omes,” such as the genome, transcriptome, proteome, and metabolome has become widespread in biomedical research. High-throughput techniques enable the rapid generation of high-dimensional multiomics data. This multiomics approach provides a more complete perspective to study biological systems compared with traditional methods. However, the quantitative analysis and integration of distinct types of high-dimensional omics data remain a challenge. Here, we provide an up-to-date and comprehensive review of the methods used for omics data quantification and integration. We first review the quantitative analysis of not only bulk but also single-cell transcriptomics data, as well as proteomics data. Current methods for reducing batch effects and integrating heterogeneous...

Xylem, the most abundant tissue on Earth, is responsible for lateral growth in plants. Typical xylem has a radial system composed of ray parenchyma cells and an axial system of fusiform cells. In most angiosperms, fusiform cells comprise vessel elements for water transportation and libriform fibers for mechanical support, while both functions are performed by tracheids in other vascular plants such as gymnosperms. Little is known about the developmental programs and evolutionary relationships of these xylem cell types. Through both single-cell and laser capture microdissection transcriptomic profiling, we determine the developmental lineages of ray and fusiform cells in stem-differentiating xylem across four divergent woody angiosperms. Based on cross-species analyses of single-cell...

Microbial communities are massively resident in the human body, yet dysbiosis has been reported to correlate with many diseases, including various cancers. Most studies focus on the gut microbiome, while the bacteria that participate in tumor microenvironments on site remain unclear. Previous studies have acquired the bacteria expression profiles from RNA-seq, whole genome sequencing, and whole exon sequencing in The Cancer Genome Atlas (TCGA). However, small-RNA sequencing data were rarely used. Using TCGA miRNA sequencing data, we evaluated bacterial abundance in 32 types of cancer. To uncover the bacteria involved in cancer, we applied an analytical process to align unmapped human reads to bacterial references and developed the BIC database for the transcriptional landscape of bacteria...

Single-cell RNA sequencing (scRNA-seq) technology allows massively parallel characterization of thousands of cells at the transcriptome level. scRNA-seq is emerging as an important tool to investigate the cellular components and their interactions in the tumor microenvironment. scRNA-seq is also used to reveal the association between tumor microenvironmental patterns and clinical outcomes and to dissect cell-specific effects of drug treatment in complex tissues. Recent advances in scRNA-seq have driven the discovery of biomarkers in diseases and therapeutic targets. Although methods for prediction of drug response using gene expression of scRNA-seq data have been proposed, an integrated tool from scRNA-seq analysis to drug discovery is required. We present scDrug as a bioinformatics...

A genetic hallmark of malignant germ cell tumours (GCTs) is isochromosome 12p, but oncogenes located in 12p that are specifically expressed in GCT have not yet been identified. SIN3-HDAC complex-associated factor (SINHCAF) is a subunit of the Sin3/histone deacetylase (HDAC) complex, and it defines a Sin3a-Hdac complex variant that is required for the self-renewal of mouse embryonic stem cells. This study demonstrated that SINHCAF is expressed in a vast majority of malignant GCTs and is rarely expressed in somatic malignancy. Fluorescence in situ hybridisation revealed SINHCAF amplification in malignant GCTs. SINHCAF silencing using shRNA reduced anchorage-dependent cell proliferation and tumoursphere formation and inhibited tumour cell migration and invasion in GCT cell lines. Moreover,...

Satisfactory treatment options for advanced leiomyosarcoma and liposarcoma are limited. The LEADER study (NCT03526679) investigated the safety and efficacy of lenvatinib plus eribulin. LEADER is a multicenter phase Ib/II study for advanced leiomyosarcoma or liposarcoma. The phase Ib part enrolled 6 patients to determine the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) with the starting dose of lenvatinib 18 mg/day and eribulin 1.1 mg/m2 D1, D8 every 21 days. The primary endpoint of the phase II part was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors 1.1, with phase Ib patients preplanned to be included in the efficacy analysis. Translational analyses were based on the transcriptomic data obtained from the NanoString nCounter...

The genome consists of non-B-DNA structures such as G-quadruplexes (G4) that are involved in the regulation of genome stability and transcription. Telomeric-repeat containing RNA (TERRA) is capable of folding into G-quadruplex and interacting with chromatin remodeler ATRX. Here we show that TERRA modulates ATRX occupancy on repetitive sequences and over genes, and maintains DNA G-quadruplex structures at TERRA target and non-target sites in mouse embryonic stem cells. TERRA prevents ATRX from binding to subtelomeric regions and represses H3K9me3 formation. G4 ChIP-seq reveals that G4 abundance decreases at accessible chromatin regions, particularly at transcription start sites (TSS) after TERRA depletion; such G4 reduction at TSS is associated with elevated ATRX occupancy and...

Nitrogen (N) and Water (W) - two resources critical for crop productivity - are becoming increasingly limited in soils globally. To address this issue, we aim to uncover the gene regulatory networks (GRNs) that regulate nitrogen use efficiency (NUE) - as a function of water availability - in Oryza sativa, a staple for 3.5 billion people. In this study, we infer and validate GRNs that correlate with rice NUE phenotypes affected by N-by-W availability in the field. We did this by exploiting RNA-seq and crop phenotype data from 19 rice varieties grown in a 2x2 N-by-W matrix in the field. First, to identify gene-to-NUE field phenotypes, we analyzed these datasets using weighted gene co-expression network analysis (WGCNA). This identified two network modules ("skyblue" & "...