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Kou, X.

Publications and source records attributed to Kou, X..

10 recordsLinked to original sources

Molecular atlas of key food odorants reveals structured aroma organization and enables generative aroma design

Food aromas arise from complex combinations of odorants, yet how these combinations are organized across foods to define aroma identity remains unclear. Decoding this "aroma code" could help bridge the sensory gap between traditional foods and sustainable alternatives, which often struggle with off-notes or to replicate consumer-expected flavor profiles. Here we present KFO-Atlas, a molecular atlas of 896 key food odorants curated from 2,282 food aroma formulations. Analysis shows that food aromas are built from sparse and structured sets of odorants. Plant-derived foods span a broad and diverse aroma space, whereas animal-derived foods tend to exhibit more similar odorant sets. In specific cases, distinct plant- and animal-based foods converge on similar odorant compositions through shared reaction pathways. Building on these insights, we develop a generative AI model that produces category-targeted aroma formulations and validate its outputs by blinded human sensory evaluation. As a proof of principle, the model reconstructs meat-like aromas using exclusively plant-derived odorants, demonstrating a data-driven route to address sensory bottlenecks in sustainable food products.

systems biology↗

Modeling Post-Gastrula Development via Bidirectional Pluripotent Stem Cells

The absence of stem cells capable of efficiently generating both trophoblast and epiblast lineages has hindered precise recapitulation of embryonic development. Through high-content chemical screening, we established an AL medium to generate mouse and human bidirectional pluripotent stem cells (BPSCs) characterized by concurrent OCT4/CDX2 expression. Mouse BPSCs demonstrated high plastic differentiation into trophoblast, epiblast and primitive endoderm lineages in vitro within 48 hours without exogenous induction factors and efficiently contributed to the embryo and extraembryonic tissues in vivo. Mechanistically, hyperactivation of the Wnt signaling pathway breaks the early lineage differentiation barrier by initiating a Lef1-dependent bypass. Remarkably, BPSCs can efficiently generated E8.5 embryoids that completed gastrulation and displayed advanced features such as brain development, a closed neural tube, a beating heart, somite formation, and primordial germ cells. These findings highlight BPSCs as a powerful tool for investigating early lineage specification and post-gastrulation embryonic development, with potential applications across multiple species.

developmental biology↗

ADNP Modulates SINE B2-Derived CTCF-Binding Sites during Blastocyst Formation in Mouse

During early embryo development, the nuclear factor CTCF plays a vital role in organizing chromatin structure and regulating transcription. Recent studies have examined the establishment of nucleosome profiles around the CTCF motif sites shortly after fertilization. However, the kinetics of CTCF chromatin occupation in pre-implantation embryos have remained unclear. In this study, we utilized CUT&RUN technology to investigate CTCF occupancy in mouse pre-implantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short-interspersed element (SINE) family B2, which are restricted to the cleavage stages. Notably, our data suggested that the neuroprotective protein ADNP may counteract the stable association of CTCF at SINE B2-derived CTCF-binding sites.

developmental biology↗

HSPA8-mediated stability of the CLPP protein regulates mitochondrial autophagy in cisplatin-resistant ovarian cancer cells

BackgroundCurrently, platinum agents remain the mainstay of chemotherapy for ovarian cancer (OC). However, cisplatin (DDP) resistance is a major reason for chemotherapy failure. Thus, it is extremely important to elucidate the mechanism of resistance to DDP. MethodsWe establish 2 DDP-resistant ovarian cancer cell lines and find that caseinolytic protease P (CLPP) is significantly downregulated in the DDP-resistant cell lines when compared to wild-type ovarian cancer cell lines (SK-OV-3 and OVcar3). Next, we investigate the functions of CLPP in the DDP-resistant and wild-type ovarian cancer cells using various assays including cell counting kit-8 assays, western blotting, immunofluorescent staining, and reactive oxygen species (ROS) and apoptosis detection. ResultsOur experiments show that CLPP knockdown significantly increase the half maximal inhibitory concentration (IC50) and mitophagy of wild-type SK-OV-3 and OVcar3 cells, while CLPP overexpression reduces the IC50 values and mitophagy of DDP-resistant SK-OV-3 and OVcar3 cells. Next, we perform database predictions and experiments to show that heat shock protein family A member 8 (HSPA8) regulates CLPP protein stability. The dynamic effects of the HSPA8/CLPP axis in the ovarian cancer cells were also examined. HSPA8 increases mitophagy and the IC50 values of SK-OV-3 and OVcar3 cells, but inhibits their ROS production and apoptosis. In addition, CLPP partly reverses the effects induced by HSPA8 in the SK-OV-3 and OVcar3 cells. ConclusionsCLPP increases the DDP resistance of ovarian cancer by inhibiting mitophagy and promoting cellular stress. Meanwhile, HSPA8 promotes the degradation of CLPP protein by inducing its stability.

cancer biology↗

Dynamic nucleosome organization after fertilization reveals regulatory factors for mouse zygotic genome activation

Chromatin remodeling is essential for epigenome reprogramming after fertilization. However, the underlying mechanisms of chromatin remodeling remain to be explored. Here, we investigated the dynamic changes in nucleosome occupancy and positioning in pronucleus-stage zygotes using ultra low-input MNase-seq. We observed distinct features of inheritance and reconstruction of nucleosome position in both paternal and maternal genomes. Genome-wide de novo nucleosome occupancy in the paternal genome was observed as early as 1 hour after the injection of sperm into ooplasm. The nucleosome positioning pattern was continually rebuilt to form nucleosome depletion regions (NDRs) at promoters and transcription factor (TF) binding sites with differential dynamics in paternal and maternal genomes. NDRs formed more quickly on the promoters of genes involved in zygotic genome activation (ZGA), and this formation is closely connected with histone acetylation, but not transcription elongation or DNA replication. Importantly, we found that NDR establishment on the binding motifs of specific TFs might be associated with their potential pioneer functions in ZGA. Further investigations suggested that the predicted factors MLX and RFX1 played important roles in regulating minor and major ZGA, respectively. Our data not only elucidate the nucleosome positioning dynamics in both male and female pronuclei following fertilization, but also provide an efficient method for identifying key transcription regulators during development.

developmental biology↗

The dual role of N6-methyladenosine on mouse maternal RNAs and 2-cell specific RNAs revealed by ULI-MeRIP sequencing

N6-methyladenosine (m6A) and its regulatory components play critical roles in various developmental processes in mammals(1-5). However, the landscape and function of m6A in the maternal-to-zygotic transition (MZT) remain unclear due to limited materials. Here, by developing an ultralow-input MeRIP-seq method, we revealed the dynamics of the m6A RNA methylome during the MZT process in mice. We found that more than 1/3 maternal decay and 2/3 zygotic mRNAs were modified by m6A. Moreover, m6As are highly enriched in the RNA of transposable elements MTA and MERVL, which are highly expressed in oocytes and 2-cell embryos, respectively. Notably, maternal depletion of Kiaa1429, a component of the m6A methyltransferase complex, leads to a reduced abundance of m6A-marked maternal RNAs, including both genes and MTA, in GV oocytes, indicating m6A-dependent regulation of RNA stability in oocytes. Interestingly, when the writers were depleted, some m6A-marked 2-cell specific RNAs, including Zscan4 and MERVL, appeared normal at the 2-cell stage but failed to be decayed at later stages, suggesting that m6A regulates the clearance of these transcripts. Together, our study uncovered that m6As function in context-specific manners during MZT, which ensures the transcriptome stability of oocytes and regulates the stage specificity of zygotic transcripts after fertilization. One Sentence Summarym6A RNA methylation stabilizes the maternal RNAs in mouse oocytes and degrades the 2-cell specific RNAs in the cleavage-stage embryos.

developmental biology↗

Apoptotic Extracellular Vesicles (ApoEVs) Safeguard Liver Homeostasis and Regeneration via Assembling an ApoEV-Golgi Organelle

Apoptosis is an integral physiological cell death process that occurs frequently and generates a huge number of apoptotic extracellular vesicles (apoEVs). However, whether apoEVs are necessary for maintaining organ homeostasis remains unclear. Here, we show that circulatory apoEVs engraft in liver and undergo specialized internalization by hepatocytes (HCs) based on surface signature of galactose and N-acetylgalactosamine. Furthermore, apoEVs rescue liver injury in apoptotic-deficient Fas mutant and Caspase-3 knockout mice, which is exerted by restoring the featured hepatic ploidy homeostasis. Surprisingly, apoEVs form a chimeric organelle complex with recipient Golgi apparatus via SNARE-mediated membrane interaction, which consequently facilitates microtubule organization and HC cytokinesis. Notably, through Golgi recovery and ploidy transition, apoEVs contribute to liver regeneration and protect against acute hepatic failure. Collectively, these results identify a previously unrecognized role for apoEVs and the specific mechanisms by which they safeguard liver homeostasis, and suggest the potential of apoEV-based therapy for liver disorders.

cell biology↗

Nuclear m6A reader Ythdc1 regulates the scaffold function of LINE1 in mouse ESCs

N6-methyladenosine (m6A) on chromosome-associated regulatory RNAs (carRNAs), including repeat RNAs, play important roles in tuning the chromatin state and transcription1. Among diverse RNA-chromatin interacting modes, the nuclear RNA scaffold is considered important for trans-interactions2,3 but has not yet been connected with m6A yet. Here, we found that Ythdc1 played indispensable roles in the embryonic stem cell (ESC) self-renewal and differentiation potency, and these roles highly depended on its m6A-binding ability. Ythdc1 deficiency in ESCs resulted in decreased rRNA synthesis and the activation of 2-cell (2C) embryo-specific transcriptional program, and these observations recapitulated the transcriptome defects induced by dysfunction of the long interspersed nuclear element-1 (LINE1)-scaffold, which were unrelated to the direct targeting of Ythdc1. A detailed analysis revealed that Ythdc1 recognized m6A on LINE1 and was physically involved in the formation of the LINE1-Nucleolin partnership and the chromatin recruitment of Kap1. In summary, our study reveals a new link between m6A and the RNA scaffold and thus provides a new regulatory model for the crosstalk between RNA and the chromatin epigenome.

cell biology↗

Comparative whole-genome analysis reveals genetic adaptation of the invasive pinewood nematode

Genetic adaptation to new environments is essential for invasive species. To explore the genetic underpinnings of invasiveness of a dangerous invasive species, the pinewood nematode (PWN) Bursaphelenchus xylophilus, we analysed the genome-wide variations of a large cohort of 55 strains isolated from both the native and introduced regions. Comparative analysis showed abundant genetic diversity existing in the nematode, especially in the native populations. Phylogenetic relationships and principal component analysis indicate a dominant invasive population/group (DIG) existing in China and expansion beyond, with few genomic variations. Putative origin and migration paths at a global scale were traced by targeted analysis of rDNA sequences. A progressive loss of genetic diversity was observed along spread routes. We focused on variations with a low frequency allele (<50%) in the native USA population but fixation in DIG, and a total of 25,992 single nuclear polymorphisms (SNPs) were screened out. We found that a clear majority of these fixation alleles originated from standing variation. Functional annotation of these SNP-harboured genes showed that adaptation-related genes are abundant, such as genes that encode for chemoreceptors, proteases, detoxification enzymes, and proteins involved in signal transduction and in response to stresses and stimuli. Some genes under positive selection were predicted. Our results suggest that adaptability to new environments plays essentially roles in PWN invasiveness. Genetic drift, mutation and strong selection drive the nematode to rapidly evolve in adaptation to new environments, which including local pine hosts, vector beetles, commensal microflora and other new environmental factors, during invasion process.

genomics↗

Genome-wide survey and expression analysis of the SLAC/SLAH gene family in pear (Pyrus bretschneideri) and other members of the Rosaceae

S-type anion channels (SLAC/SLAHs), which play important roles in plant anion (such as nitrate and chloride) transport, growth and development, abiotic stress responses and hormone signaling. However, there is far less information about this family in Rosaceae species. We performed a genome-wide analysis and identified SLAC/SLAH gene family members in pear (Pyrus bretschneideri) and four other species of Rosaceae (Malus domestica, Prunus persica, Fragaria vesca and Prunus mume). A total of 21 SLAC/SLAH genes were identified from the five Rosaceae species. Based on the structural characteristics and a phylogenetic analysis of these genes, the SLAC/SLAH gene family could be classified into three main groups (I, II and III). The evolutionary analysis showed that the SLAC/SLAH gene family was comparatively conserved during the evolution of Rosaceae species. Transcriptome data demonstrated that PbrSLAC/SLAH genes were detected in all parts of the pear. However, PbrSLAC1 showed a higher expression level in leaf, while PbrSLAH2/3 was mainly expressed in roots. In addition, PbrSLAC/SLAH genes were only located on the plasma membrane in transient expression experiments in Arabidopsis protoplasts cells. These results provide valuable information that increases our understanding of the evolution, expression and functions of the SLAC/SLAH gene family in higher plants.

bioinformatics↗