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"Yang, Gui"
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Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.
Journal Article
5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs
Although 5-methylcytosine (m
5
C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m
5
C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m
5
C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m
5
C ‘reader’ recognizing m
5
C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m
5
C methylation site in the
HDGF
3′ untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m
5
C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.
Chen et al. provide an m
5
C landscape in bladder cancer and show m
5
C enrichment at oncogene mRNAs that promotes tumour progression. They identify YBX1 as the m
5
C ‘reader’ that recruits ELAVL1 to stabilize mRNAs.
Journal Article
Cancer Stem Cells (CSCs) in Drug Resistance and their Therapeutic Implications in Cancer Treatment
Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are suggested to be responsible for drug resistance and cancer relapse due in part to their ability to self-renew themselves and differentiate into heterogeneous lineages of cancer cells. Thus, it is important to understand the characteristics and mechanisms by which CSCs display resistance to therapeutic agents. In this review, we highlight the key features and mechanisms that regulate CSC function in drug resistance as well as recent breakthroughs of therapeutic approaches for targeting CSCs. This promises new insights of CSCs in drug resistance and provides better therapeutic rationales to accompany novel anticancer therapeutics.
Journal Article
Duckweed Is a Promising Feedstock of Biofuels: Advantages and Approaches
With the growing scarcity of traditional sources of energy and the accompanying acute environmental challenges, biofuels based on biomass are favored as the most promising alternative. As one of the core raw materials for biomass energy, research on its production methods and synthesis mechanisms is emerging. In recent years, duckweed has been used as a high-quality new biomass feedstock for its advantages, including fast biomass accumulation, high starch content, high biomass conversion efficiency, and sewage remediation. This study provides a systematic review of the growth characteristics, starch metabolism pathways, and methods to improve starch accumulation in the new energy plant, duckweed. The study also presents a prospect that might be used as a reference for the development of duckweed as a new energy-providing plant.
Journal Article
Single-cell transcriptome profiling of the vaginal wall in women with severe anterior vaginal prolapse
Anterior vaginal prolapse (AVP) is the most common form of pelvic organ prolapse (POP) and has deleterious effects on women’s health. Despite recent advances in AVP diagnosis and treatment, a cell atlas of the vaginal wall in AVP has not been constructed. Here, we employ single-cell RNA-seq to construct a transcriptomic atlas of 81,026 individual cells in the vaginal wall from AVP and control samples and identify 11 cell types. We reveal aberrant gene expression in diverse cell types in AVP. Extracellular matrix (ECM) dysregulation and immune reactions involvement are identified in both non-immune and immune cell types. In addition, we find that several transcription factors associated with ECM and immune regulation are activated in AVP. Furthermore, we reveal dysregulated cell–cell communication patterns in AVP. Taken together, this work provides a valuable resource for deciphering the cellular heterogeneity and the molecular mechanisms underlying severe AVP.
Anterior vaginal prolapse (AVP), the most common form of pelvic organ prolapse, has deleterious effects on women’s health. Here the authors employ single-cell RNA-seq to construct a transcriptomic atlas of vaginal wall cells from AVP patients, and find that extracellular matrix dysregulation and immune reaction are associated with AVP.
Journal Article
Surface chelation of cesium halide perovskite by dithiocarbamate for efficient and stable solar cells
Surface engineering has been shown critical for the success of perovskite solar cells by passivating the surface enriched defects and mobile species. The discovery of surface modulators with superior interaction strength to perovskite is of paramount importance since they can retain reliable passivation under various environments. Here, we report a chelation strategy for surface engineering of CsPbI
2
Br perovskite, in which dithiocarbamate molecules can be coordinate to surface Pb sites via strong bidentate chelating bonding. Such chelated CsPbI
2
Br perovskite can realize excellent passivation of surface under-coordinated defects, reaching a champion power conversion efficiency of 17.03% and an open-circuit voltage of 1.37 V of CsPbI
2
Br solar cells. More importantly, our chelation strategy enabled excellent device stability by maintaining 98% of their initial efficiency for over 1400 h in ambient condition. Our findings provide scientific insights on the surface engineering of perovskite that can facilitate the further development and application of perovskite optoelectronics.
Surface engineering is a known strategy to optimize the perovskite solar cells but it is usually based on weak bondings, such as Van der Waals, or coorordiating interacterions. Here He et al. report a chelation strategy using strongly adsorbed dithiocarbamate molecules and achieve high efficiency of 17.03% with excellent stability for CsPbI
2
Br based solar cells.
Journal Article
Cytoplasmic m6A reader YTHDF3 promotes mRNA translation
Dear Editor, N6-methyladenosine （m6A）, as the most abundant internal modification with ubiquitous feature in eukaryotic mRNAs, has been connected with many fundamental aspects of RNA metabolism such as translation [1-3], splicing [4, 5], stability and decay [6]. m6A modification is reversible and can be regulated by three groups of molecules commonly referred to as writers, erasers and readers, m6A writers are the components of the multi-complex methyltransferase catalyzing the formation of m6A methylation, among which METTL3,
Journal Article
FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis
The role of Fat Mass and Obesity-associated protein （FTO） and its substrate N6-methyladenosine （m6A） in mRNA processing and adipogenesis remains largely unknown. We show that FTO expression and m6A levels are inversely correlated during adipogenesis. FTO depletion blocks differentiation and only catalytically active FTO restores adi- pogenesis. Transcriptome analyses in combination with m6A-seq revealed that gene expression and mRNA splicing of grouped genes are regulated by FTO. M6A is enriched in exonic regions flanking 5＇- and 3＇-splice sites, spatially over- lapping with mRNA splicing regulatory serine/arginine-rich （SR） protein exonic splicing enhancer binding regions. Enhanced levels of m6A in response to FTO depletion promotes the RNA binding ability of SRSF2 protein, leading to increased inclusion of target exons. FTO controls exonic splicing of adipogenie regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation. These findings provide compelling evidence that FTO-dependent m6A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis.
Journal Article
Nitrogen fertilization coupled with iron foliar application improves the photosynthetic characteristics, photosynthetic nitrogen use efficiency, and the related enzymes of maize crops under different planting patterns
Photosynthetic rate (Pn) and photosynthetic nitrogen use efficiency (PNUE) are the two important factors affecting the photosynthesis and nutrient utilization of plant leaves. However, the effect of N fertilization combined with foliar application of Fe on the Pn and PNUE of the maize crops under different planting patterns (i.e., monocropping and intercropping) is elusive. Therefore, this experiment was conducted to determine the effect of N fertilization combined with foliar application of Fe on the photosynthetic characteristics, PNUE, and the associated enzymes of the maize crops under different planting patterns. The results of this study showed that under intercropping, maize treated with N fertilizer combined with foliar application of Fe had not only significantly ( p < 0.05) improved physio-agronomic indices but also higher chlorophyll content, better photosynthetic characteristics, and related leaf traits. In addition, the same crops under such treatments had increased photosynthetic enzyme activity (i.e., rubisco activity) and nitrogen metabolism enzymes activities, such as nitrate reductase (NR activity), nitrite reductase (NiR activity), and glutamate synthase (GOGAT activity). Consequently, intercropping enhanced the PNUE and soluble sugar content of the maize crops, thus increasing its yield compared with monocropping. Thus, these findings suggest that intercropping under optimal N fertilizer application combined with Fe foliation can improve the chlorophyll content and photosynthetic characteristics of maize crops by regulating the associated enzymatic activities. Consequently, this results in enhanced PNUE, which eventually leads to better growth and higher yield in the intercropping system. Thus, practicing intercropping under optimal nutrient management (i.e., N and Fe) could be crucial for better growth and yield, and efficient nitrogen use efficiency of maize crops.
Journal Article