Biology subjects

Shi, M.

Publications and source records attributed to Shi, M..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

Comparative Transcriptomic Analysis of Embryonic Stem Cells (ESCs) across Mammalian Species

Pluripotency, the ability of cells to self-renew and differentiate into all the cell types in an animals body, is vital for mammalian early development. This study presented a comprehensive comparative transcriptomic analysis of embryonic stem cells across multiple mammalian species, defining their progression through expanded/extended, naive, formative, and primed pluripotency states. Our findings revealed both conserved and species-specific mechanisms underlying pluripotency regulation. We also emphasized the limitations of existing state-specific markers and their limited cross-species applicability, while identifying de novo pluripotency markers that can inform future research. Despite variability in gene expression dynamics, gene co-expression networks showed remarkable conservation across species. Among pluripotency states, the primed state demonstrated the highest conservation, evidenced by shared markers, preserved gene networks, and stronger selective pressures acting on its genes. These findings provide critical insights into the evolution and regulation of pluripotency, laying a foundation for refining stem cell models to enhance their translational potential in regenerative medicine, agriculture, and conservation biology.

genomics↗

bioRxiv2025

Sex-biased Transcriptome in in vitro Produced Bovine Early Embryos

BackgroundMorphologic sex differences between males and females typically emerge after the primordial germ cell migration and gonad formation, although sex is determined at fertilization based on chromosome composition. A key debated sexual difference is the embryonic developmental rate, with in vitro produced male embryos often developing faster. However, the molecular mechanisms driving early embryonic sex differences remain unclear. ResultsTo investigate the transcriptional sex difference during early development, in vitro produced bovine blastocysts were collected and sexed by PCR. A significant male-biased development was observed in expanded blastocysts. Ultra-low input RNA-seq analysis identified 837 DEGs, with 231 upregulated and 606 downregulated in males. Functional enrichment analysis revealed male-biased DEGs were associated with metabolic regulation, whereas female-biased DEGs were related to female gonad development, sex differentiation, inflammatory pathways, and TGF-beta signaling. Comparing X chromosome and autosome expression ratio, we found that female-biased DEGs contributed to the higher X-linked gene dosage, a phenomenon not observed in male embryos. Moreover, we identified the sex-biased transcription factors and RNA-bind proteins, including pluripotent factors such as SOX21 and PRDM14, and splicing factors FMR1 and HNRNPH2. Additionally, we revealed 1,555 significantly sex-biased differential alternative splicing (AS), predominantly skipped exons, mapped to 906 genes, with 59 overlapping with DEGs enriched in metabolic and autophagy pathways. By incorporating novel isoforms from long reads sequencing, we identified 1,151 sex-biased differentially expressed isoforms (DEIs) associated with 1,017 genes. Functional analysis showed that female-biased DEIs were involved in the negative regulation of transcriptional activity, while male-biased DEIs were related to energy metabolism. Furthermore, we identified sex-biased differential exon usage in DENND1B, DIS3L2, DOCK11, IL1RAPL2, and ZRSR2Y, indicating their sex-specific regulation in early embryo development. ConclusionThis study provided a comprehensive analysis of transcriptome differences between male and female bovine blastocysts, integrating sex-biased gene expression, alternative splicing, and isoform dynamics. Our findings indicate that enriched metabolism processes in male embryos may contribute to the faster developmental pace, providing insights into sex-specific regulatory mechanisms during early embryogenesis. Plain English summaryMale and female early embryos develop at different speeds, with male embryos often developing faster than female embryos. However, the reasons behind these early differences remain unclear. In this study, we examined gene activity in bovine embryos to uncover the biological factors regulating these early sex differences. We collected in vitro-produced bovine blastocysts, examined their sex, and confirmed that male embryos develop faster. By analyzing global gene activity, including alternative splicing, which allows one gene to code for multiple RNA isoforms and proteins, we found distinct gene expression profiles between male and female embryos. Male embryos showed higher activity in genes related to metabolism and cellular functions, while female embryos had increased activity in genes associated with female-specific gonad development and gene expression regulation. We also examined differences in how genes on the X chromosome were expressed. Female embryos had higher X-linked gene expression, which may contribute to sex-specific developmental regulation. Additionally, we identified sex-specific transcription factors and RNA-binding proteins that regulate early embryo development, some of which are known to control pluripotency and gene splicing. Overall, our study provides new insights into how gene activity shapes early sex differences, suggesting that enhanced metabolism in male embryos may be a key driver of their faster developmental rate. HighlightsO_LIMale embryos develop faster due to increased gene expression in metabolism pathways C_LIO_LIFemale embryos exhibit higher X-linked gene expression, suggesting X-dosage compensation plays a role in early development C_LIO_LISex-biased alternative splicing events contribute to embryonic metabolism, autophagy, and transcriptional regulation in embryos C_LIO_LISex-biased isoform diversity contributes to distinct developmental regulation in male and female embryos C_LIO_LIKey pluripotency factors (SOX21, PRDM14) and splicing regulators (FMR1, HNRNPH2) drive sex-specific gene expression C_LI

developmental biology↗

bioRxiv2025

Transgenerational effects of perinatal cannabis exposure on female reproductive parameters in mice

The use of cannabis during pregnancy and nursing is a growing public health concern, and the multigenerational impacts of perinatal cannabis exposure remain largely unknown. To address this knowledge gap, we sought to examine the long-term consequences of perinatal cannabis use on reproductive function and how it might impact subsequent generations. Pregnant female mice were exposed to control vehicle or cannabis extract [25, 100, or 200 mg/ml {Delta}9-tetrahydrocannabinol (THC) in the cannabis extract] from gestational day 1 to postnatal day 21 (twice/day), encompassing the duration of pregnancy through weaning. Based on plasma THC concentrations in F0 females, we chose 100 and 200 mg/ml THC in the cannabis extract for subsequent studies. The selected doses and exposure conditions did not disrupt pregnancy or nursing in F0 females. Pregnancy and neonatal outcomes, including gestational length, litter size, and sexual ratio, were not affected by cannabis exposure. However, cannabis-exposed neonatal F1 pups were smaller. Cannabis exposure delayed vaginal opening as a sign of puberty onset and disrupted estrous cyclicity in F1 females. However, its effects were minor in F2 and F3 females. F1-F3 females showed no abnormal ovarian and uterine histology or plasma estradiol-17{beta} levels and could produce normal offspring without pregnancy issues. These results suggest that the hypothalamus and pituitary are likely perturbed by perinatal cannabis exposure, and the early hypothalamus-pituitary-ovarian axis is disrupted in F1 females. However, they are not sufficient to compromise adult reproductive function. The present results indicate limited transgenerational effects of perinatal cannabis exposure on female reproductive parameters.

pharmacology and toxicology↗

bioRxiv2025

Promoter-centric gene regulation in drug-resistant cancer

In eukaryotic cells, gene-distal regulatory elements (REs) facilitate long-range gene regulation, ensuring cell type-specific transcriptional programs. This mechanism is frequently disrupted in cancer, often driven by transcription factors (TFs) that serve as targets for cancer therapy. However, targeting these TFs can lead to acquired resistance mechanisms that are not fully understood. We demonstrate that mesothelioma cancer cells, dependent on the oncogenic driver TF family TEAD, develop resistance to a pan-TEAD inhibitor and revert to an evolutionarily ancient, promoter-centric gene regulatory mechanism to recover gene expression following TEAD inhibition. Base-pair-resolution 3D chromatin conformation mapping reveals that RE-promoter interactions are disrupted in resistant cells, despite epigenetic and transcriptomic recovery. Mechanistically, in resistant cells, TF complexes, including resistance-specific FOSL1 and KLF4, preferentially bind and enhance promoter activity to recover gene expression, rendering distal REs dispensable. Our findings highlight promoter elements and promoter-specific TFs as potential therapeutic targets using a model of drug-resistant cancer.

cancer biology↗

bioRxiv2025

Infectome Analysis of Small Mammals in Southern China Reveals Ecological Associations and Emerging Threats from Diverse Pathogens

Small mammals harbor a diverse array of zoonotic pathogens. To date, however, metagenomic surveys of these species have primarily focused on viral diversity, with limited attention paid to bacteria and eukaryotic pathogens. Additionally, the ecological determinants of pathogen diversity within these mammals have not been systematically examined. Herein, we employed a metatranscriptomics approach to survey the pathogen infectome of 2,408 individual samples, representing lung, liver, and gut tissues from 858 animals collected throughout Guangdong province, China, with a study design that accounted for host species, tissue, season, and geographic location. We identified 76 pathogen species, including 29 RNA viruses, 12 DNA viruses, 5 bacteria, and 30 eukaryotic pathogens, 33 of which were newly discovered. Tissue distribution analysis revealed distinct organotropisms, suggesting varied transmission routes, while host distribution analysis showed that each animal carried an average of one pathogen, with 10 pathogens widely distributed among mammalian orders. Our characterization of the geographic and seasonal patterns revealed that pathogen richness was primarily influenced by region, host species, and season, while pathogen composition was largely shaped by host genetic distance. Collectively, these data provide the first comprehensive insight into the dynamics of the pathogen infectome in these key mammalian disease reservoirs, highlighting the major factors driving pathogen diversity and transmission.

microbiology↗

bioRxiv2025

Multiple lesion inductions intensify central sensitization driven by neuroinflammation in a mouse model of endometriosis.

IntroductionEndometriosis is an inflammatory disease associated with chronic pelvic pain (CPP). Growing evidence indicates that endometriotic lesions are not the sole source of pain. Instead, central nervous system (CNS) dysfunction created by prolonged peripheral and central sensitization plays a role in developing endometriosis-associated CPP. This study investigated how CPP is established using a multiple lesion induction mouse model of endometriosis, as repeated retrograde menstruation is considered underlying endometriosis pathogenesis. MethodsWe generated endometriosis-like lesions by injecting endometrial tissue fragments into the peritoneal cavity in mice. The mice received a single (1x) or multiple inductions (6x) to simulate recurrent retrograde menstruation. Lesion development, hyperalgesia by behavioral testing, signs of peripheral sensitization, chronic inflammation, and neuroinflammation were examined with lesions, peritoneal fluids, dorsal root ganglia (DRG), spinal codes, and brain. ResultsMultiple lesion inductions increased lesion numbers and elevated abdominal and hind paw hypersensitivity compared to single induction mice. Elevated persistent glial cell activation across several brain regions and/or spinal cords was found in the multiple induction mice. Specifically, IBA1+ microglial soma size was increased in the hippocampus and thalamus. IBA1+ cells were abundant in the cortex, hippocampus, thalamus, and hypothalamus of the multiple induction mice. GFAP+ astrocytes were mainly elevated in the hippocampus. Elevated TRPV1, SP, and CGRP expressions in the DRG were persistent in the multiple induction mice. Furthermore, multiple inductions induced the severe disappearance of TIM4hi MHCIIlo residential macrophages and the influx of increased proinflammatory TIM4lo MHCIIhi macrophages in the peritoneal cavity. The single and multiple inductions elevated secreted TNF, IL-1{beta}, and IL-6 levels in the peritoneal cavity at 2 weeks. Elevated cytokine levels returned to the pre-induction levels in the single induction mice at 6 weeks; however, they remained elevated in the multiple induction mice. ConclusionsOur results indicate that the repeatedly occurring lesion inductions (=mimic retrograde menstruation) can be a peripheral stimulus that induces nociceptive pain and creates composite chronic inflammatory stimuli to cause neuroinflammation and sensitize the CNS. The circuits of neuroplasticity and stimulation of peripheral organs via a feedback loop of neuroinflammation may mediate widespread endometriosis-associated CPP.

molecular biology↗

bioRxiv2025

Infectome analysis of bat kidneys from Yunnan province, China, reveals close relatives of Hendra-Nipah viruses and prevalent bacterial and eukaryotic pathogens

Bats are natural reservoirs for a wide range of microorganisms, including many notable zoonotic pathogens. However, the infectome of bat kidneys remains poorly understood. To address this gap, we performed meta-transcriptomic sequencing on kidney tissues from 142 bats, spanning ten species sampled at five locations in Yunnan province, China. This analysis identified 22 viral species, including 20 novel viruses, two of which represented newly discovered henipaviruses closely related to the highly pathogenic Hendra and Nipah viruses. These henipaviruses were found in the kidneys of bats inhabiting an orchard near villages, raising concerns about potential fruit contamination via bat urine and transmission risks to livestock or humans. Additionally, we identified a novel protozoan parasite, tentatively named Klossiella yunnanensis, along with two highly abundant bacterial species, one of which is a newly discovered species--Flavobacterium yunnanensis. These findings broaden our understanding of the bat kidney infectome, underscore critical zoonotic threats, and highlight the need for comprehensive, full-spectrum microbial analyses of previously understudied organs to better assess spillover risks from bat populations.

microbiology↗

bioRxiv2025

Comprehensive Infectome Analysis Reveals Diverse Infectious Agents with Zoonotic Potential in Wildlife

Understanding wildlife-pathogen interactions is crucial for mitigating zoonotic risk. Through meta-transcriptomic sequencing we profiled the infectomes of 1,922 samples from 67 mammalian species across China, uncovering a remarkable diversity of viral, bacterial, fungal, and parasitic pathogens. Of the 195 pathogens identified, 62 were novel, including a bi- segmented coronavirus in diseased lesser pandas, which we propose represents a new genus - Zetacoronavirus. The orders Carnivora and Rodentia exhibited the highest pathogen diversity and were implicated in numerous host-jumping events. Comparative analysis of diseased versus healthy animals revealed a trend of higher pathogen loads in the former, with possible differences in tissue tropisms. In total, 48 zoonotic and 17 epizootic pathogens were identified, with frequent cross-species transmission, emphasizing the potential for emerging public health threats. This study highlights the urgent need for wildlife pathogen surveillance to inform proactive disease management strategies.

microbiology↗

bioRxiv2024

Elastase mediated white matter damage in cerebral small vessel disease: Microglia - neutrophils pas de deux

Cerebral small vessel disease (CSVD) leads to an extensive white matter damage associated with cognitive decline, yet the underlying damaging mechanisms remain incompletely understood. Here we established a positive correlation between plasma levels of serine proteinase elastase ELANE and periventricular white matter hyperintensity (PV-WMH) in a cohort of CSVD patients. In a CSVD murine model induced by bilateral carotid artery stenosis (BCAS), upregulated ELANE was detected both in microglia and peripheral blood neutrophils. Genetic ELANE deficiency significantly alleviated oligodendrocyte loss, thereby reducing white matter lesions (WMLs) as well as ameliorating sensorimotor and cognitive impairments in BCAS mice. In vitro studies demonstrated that ELANE triggered time-dependent and dose-dependent oligodendrocyte lineage cell death. Bone marrow transplantation showed that ELANE from microglia and peripheral blood both contributed to WML development and BCAS-induced neurological deficits. Mechanistically, ELANE, accumulated by oligodendrocytes, cleaved the phosphodiesterase domain of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase). Pharmacological inhibition of ELANE with Sivelestat reduced oligodendrocyte loss and WMLs leading to the restoration of white matter integrity and neurological improvements in BCAS mice. In post-mortem brain specimens of CSVD patients ELANE accumulated within WMLs being predominantly localized in microglia (and hence defined as microglial ELANE) rather than in the brain-infiltrating neutrophils. We therefore posit microglial ELANE as an instigator of whiter matter injury in CSVD and suggest its potential therapeutic relevance.

neuroscience↗

bioRxiv2024

Comparative atlas of genome-wide chromatin-associated protein co-occupancy

Accurate transcriptional regulation and chromatin dynamics requires the coordination and activity of chromatin-associated proteins (CAPs) at distinct loci. While the combinatorial activity of a select set of CAPs has been previously examined, these studies are limited by the underrepresentation of proteins and cell types explored, making it difficult to identify the global associations as well as the conservation of these associations across different cell types. Here, we performed 270 CAP chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) experiments in both K562 and HepG2 cancer cell lines and explored the relationship between cell identity and CAP co-association using three distinct approaches. We employed a machine learning algorithm to organize the genome-wide binding profiles into 56 and 70 interpretable co-association modules for HepG2 and K562 cell lines, respectively. We found CAP co-association modules are mostly cell type-specific, however those present in both cell lines are largely comprised of TFs from a single TF family and anchor to unique loci via lineage-specific factors. While enhancer-associated co-binding modules were largely composed of cell type-specific CAPs, we found regulatory activity at promoter-enhancer module contacts to be enriched for chromatin remodeling proteins. Additionally, we used colocalization information derived from co-association models in conjunction with neural network models of transcription factor (TF) activity to identify high-confidence candidate TF cooperative pairs. Finally, through comparing CAP enrichment in high occupancy target (HOT) regions in K562 and HepG2 cell lines, we found cell type-specific HOT sites, but not common HOT sites, are selectively enriched at high copy number loci. Overall, this study uncovers principles of sequence-level and large-scale CAP genomic organization and demonstrates how this contributes to cell type-specific regulatory mechanisms and cellular functions.

genomics↗

bioRxiv2024

Tunicate metatranscriptomes reveal ancient virus-host co-divergence and inter-order recombination in the evolutionary history of disease-causing viruses

Tunicates are a key transitional taxon in animal evolution as the closest extant invertebrate relatives of the vertebrates. Their viruses may also reflect this transitional state. Yet, it is not known whether tunicate viruses are more closely related to vertebrate- or invertebrate-infecting viral lineages. We analysed primary and publicly available RNA libraries to extend the known diversity of tunicate-associated viruses and determine their relationship to viruses of other animals. We present evidence that influenza viruses, alphaviruses, and some mononegaviruses emerged prior to the evolution of vertebrates. We also show that the recombination of glycoproteins between different orders of RNA viruses, including between positive- and negative-sense viruses, may have shaped the evolution of multiple lineages. Our study reveals that some disease-causing RNA virus lineages were present in early chordates and highlights that the evolution of structural genes may be incongruent with that of the highly conserved RNA-dependent RNA polymerase.

microbiology↗

bioRxiv2024

Assessment of DNA methylation from a single genomic region of ELOV2 is sufficient to predict chronological age

Estimation of chronological age is particularly informative in forensic contexts. Assessment of DNA methylation status allows for the prediction of age, though the accuracy and ease of manipulation may vary across different models. In this study, we started with a carefully designed discovery cohort recruiting more elderly subjects than other age categories, to diminish the effect of epigenetic drifting. We analyzed DNA methylation from a single genomic region of ELOV2, which was sufficient to construct an age-prediction model comprising 15 CpG sites. This model is further validated by an independent cohort as well as a multi-center test using trace dried bloodstains. The nature of our analytical pipeline, when combined the assessment of a single genomic locus with high-throughput sequencing, can easily be scaled up with low cost. Taken together, we propose a new age-prediction model featuring accuracy, ease of manipulation, high-throughput, and low cost. This model can be readily applied in both classic and newly emergent forensic contexts that require age estimation.

genetics↗

bioRxiv2024

Near-infrared real time non-destructive monitoring of sugar accumulation reveals that single berries ripen two times faster than previously documented on standard asynchronous samples

Understanding how climate change impacts berry ripening physiology is essential for selecting genotypes that balance sugars and acids under warming conditions. In this context, we used a portable near-infrared spectrometer in the vineyard, to monitor sugar and acid evolution in individual berries from 10 grapevine varieties over two years. Spectra were periodically acquired on the same berries all along ripening, and a subset of these berries was also collected for sugars and organic acids quantification by HPLC, to train partial least square regression models. Prediction models for glucose, fructose, and malic acid concentrations were characterized by validation R{superscript 2} of 0.71, 0.64, and 0.55, respectively. We further used these models to follow sugar accumulation in individual berries and observed that single berries ripen two times faster than found in samples composed of multiple berries. Our results pave avenues toward precise quantitative approaches on sugar and acid fluxes in berry ripening studies.

plant biology↗

bioRxiv2024

Environmentally-relevant doses of bisphenol A and S exposure in utero disrupt germ cell programming across generations resolved by single nucleus multi-omics

BackgroundExposure to endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), disrupts reproduction across generations. Germ cell epigenetic alterations are proposed to bridge transgenerational reproductive defects resulting from EDCs. Previously, we have shown that prenatal exposure to environmentally relevant doses of BPA or its substitute, BPS, caused transgenerationally maintained reproductive impairments associated with neonatal spermatogonial epigenetic changes in male mice. While epigenetic alterations in germ cells can lead to transgenerational phenotypic variations, the mechanisms sustaining these changes across generations remain unclear. ObjectivesThis study aimed to systematically elucidate the mechanism of transgenerational inherence by prenatal BPA and BPS exposure in the murine germline from F1 to F3 generations at both transcriptomic and epigenetic levels. MethodsBPA or BPS with doses of 0 (vehicle control), 0.5, 50, or 1000 {micro}g/kg/b.w./day was orally administered to pregnant CD-1 females (F0) from gestational day 7 to birth. Sperm counts and motility were examined in F1, F2, and F3 adult males. THY1+ germ cells on postnatal day 6 from F1, F2, and F3 males at a dose of 50 {micro}g/kg/b.w./day were used for analysis by single-nucleus (sn) multi-omics (paired snRNA-seq and snATAC-seq on the same nucleus). ResultsPrenatal exposure to BPA and BPS with 0.5, 50, and 1000 {micro}g/kg/b.w./day reduced sperm counts in mice across F1 to F3 generations. In the F1 neonatal germ cells, ancestral BPA or BPS exposure with 50 {micro}g/kg/b.w./day resulted in increased differentially expressed genes (DEGs) associated with spermatogonial differentiation. It also disrupted the balance between maintaining the undifferentiated and differentiating spermatogonial populations. Differentially accessible peaks (DAPs) by snATAC-seq were primarily located in the promoter regions, with elevated activity of key transcription factors, including SP1, SP4, and DMRT1. Throughout F1-F3 generations, biological processes related to mitosis/meiosis and metabolic pathways were substantially up-regulated in BPA-or BPS-exposed groups. While the quantities of DEGs and DAPs were similar in F1 and F2 spermatogonia, with both showing a significant reduction in F3. Notably, approximately 80% of DAPs in F1 and F2 spermatogonia overlapped with histone post-translational modifications linked to transcription activation, such as H3K4me1/2/3 and H3K27ac. Although BPA exerted more potent effects on gene expression in F1 spermatogonia, BPS induced longer-lasting effects on spermatogonial differentiation across F1 to F3 males. Interestingly, DMRT1 motif activity was persistently elevated across all three generations following ancestral BPA or BPS exposure. DiscussionOur work provides the first systematic analyses for understanding the transgenerational dynamics of gene expression and chromatin landscape following prenatal exposure to BPA or BPS in neonatal spermatogonia. These results suggest that prenatal exposure to environmentally relevant doses of BPA or BPS alters chromatin accessibility and transcription factor motif activities, consequently contributing to disrupted transcriptional levels in neonatal germ cells, and some are sustained to F3 generations, ultimately leading to the reduction of sperm counts in adults.

pharmacology and toxicology↗

bioRxiv2024

Multi-omics analysis of the mechanism of alfalfa and wheat-induced rumen flatulence in Xizang sheep

This study induced a rumen flatulence model in Xizang sheep using alfalfa (HRF) and wheat grass (MRF) to explore related mechanisms. The pH of HRF and MRF groups was lower than the natural grass group. SCFA concentrations varied in different groups. Microbial analysis showed HRF and MRF groups had lower alpha and beta diversity and different compositions. Transcriptome analysis found different numbers of differentially expressed genes in each group. Spearmans correlation analysis indicated Butyrivibrio was related to GLRX and DUOX2, and Quinella to several genes.

microbiology↗

bioRxiv2024

Efficient degradation of oxidized polyethylene containing ester bonds by cutinase or lipase in aqueous phase

Polyethylene (PE) plastics are extensively utilized across agricultural, industrial, and medical sectors owing to their favorable physicochemical properties. However, their chemical stability and escalating production have resulted in severe waste accumulation and environmental pollution. Conventional disposal methods are plagued by resource inefficiency and secondary pollution. While emerging strategies offer promise, physicochemical methods demand harsh operating conditions, and biological routes remain inefficient. This research presents an integrated "chemical pretreatment-biodegradation-upcycling" system that combines the efficiency of chemical catalysis with the sustainability of biological conversion. Ester bonds were introduced into PE via Baeyer-Villiger oxidation, followed by enzymatic hydrolysis using the cutinase from Thermobifida fusca WSH03-11 (TfCut). Specifically, machine learning-aided optimization of reaction conditions and computational redesign of TfCut enhanced degradation efficiency, yielding a maximum weight loss of approximately 71.19%. The degradation intermediates were bio-converted into poly(3-hydroxybutyrate) (PHB) by the wild-type strain LETBE-HOU, isolated in this study, achieving a concentration of 16.75 mg/L. Multi-omics analysis of LETBE-HOU further revealed the PHB biosynthesis pathway and fatty acid degradation regulation. This work breaks the long-standing reliance on physiochemically-derived degradation intermediates for microbial conversion of PE, establishing a fully circular system that opens new avenues for future research.

biochemistry↗

bioRxiv2024

Time-resolved transcriptomic of single V. vinifera fruits: membrane transports as switches of the double sigmoidal growth

By revealing that the grape berry loses one H+ per accumulated sucrose at the inception of ripening, adopting a single fruit paradigm elucidates the fundamentals of the malate-sugar nexus, previously obscured by asynchrony in population-based models of ripening. More broadly, the development of the individual fruit was revisited from scratch to capture the simultaneous changes in gene expression and metabolic fluxes in a kinetically relevant way from flowering to overripening. Dynamics in water, tartrate, malate, hexoses, and K+ fluxes obtained by combining individual single fruit growth and concentration data allowed to define eleven sub-phases in fruit development, which distributed on a rigorous curve in RNAseq PCA. WGCNA achieved unprecedented time resolutions in exploring transcript level-metabolic rate associations. A comprehensive set of membrane transporters was found specifically expressed during the first growth phase related to vacuolar over-acidification. Unlike in slightly more acidic citrus, H+ V-PPase transcripts were predominantly expressed, followed by V-ATPase and PH5, clarifying the thermodynamic limit beyond which replacement by the PH1/PH5 complex turns compulsory. Puzzlingly, bona fide ALMT kept a low profile at this stage, possibly replaced by a predominating uncharacterized anion channel. Then, the switch role of HT6 in sugar accumulation was confirmed, electroneutralized by malate vacuolar leakage and H+ pumps activation. HighlightsTo alleviate asynchronicity biases, transcripts showing strict coincidental timing with pericarp physiological phases were disentangled on single berries, enlightening the tight multifaceted membrane developmental control of sugar and acid fluxes.

plant biology↗

bioRxiv2024

FishCODE: a web-based information platform for comprehensive omics data exploration in fish research

In terms of the utilization of omics data, the current fish database analysis functions are primarily relatively simple tools at the transcriptional level, aimed at obtaining the co-expression levels of specified genes or the data visualization of multiple genes, and do not enable users to perform comprehensive omics data analysis. Furthermore, the gene-level information currently provided by these multispecies fish genomics databases is incomplete, and there is a lack of a comprehensive portal that can offer multidimensional genetic information. To address these challenges, we collected extensive multi-omics information on 35 fishes and established the primary comprehensive multi-omics data information platform for fish, FishCODE (http://bioinfo.ihb.ac.cn/fishcode). We have collected experimental background of dataset which pertaining to the target fishes, selected a range of datasets that encompass a broad spectrum of research areas, and downloaded the corresponding raw omics data from public repositories such as the Sequence Read Archive (SRA). Through a unified pipeline analysis, FishCODE contains 11,216 samples from 540 sets of genomic, transcriptomic, and methylomic datasets. These data encompass transcript structure and expression, gene methylation levels, protein domains, protein subcellular localization, protein interactions, best matched protein (Swiss-Prot), associated SNP site information (47,111,018), orthologous genes, phylogenetic tree and GO/KEGG annotations. To facilitate comparison, we annotated the experimental background data sets of the FishCODE, FishGET, PhyloFish, FishSED and FishSCT databases using the Fish Experimental Condition Ontology. Currently, the FishCODE database omics dataset includes 146 unique experimental condition words, 654 cumulative experimental condition words, and 13 species with rich experimental background (more than 20 unique FECO words). These data are 3.5 times (42), 8.3 times (74), and 6.5 times (2) those of the second-ranked databases respectively. We generated word cloud maps for the experimental condition vocabularies of FishCODE and FishGET, illustrating the superior richness of FishCODEs experimental background.

bioinformatics↗