Biology subjects

Tong, C.

Publications and source records attributed to Tong, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Evolutionary and multi-omic divergences associated with the extreme sexual size dimorphism in spiders

Extreme sexual size dimorphism (SSD) represents one of the most striking forms of phenotypic divergence between the sexes, yet the genomic basis of extreme body-size dimorphism remains poorly understood. Orb-weaving spiders exhibit some of the most pronounced female-biased SSD among terrestrial arthropods, providing an exceptional system for investigating the evolutionary and genomic changes associated with extreme SSD. Here, we combined comparative genomics across 51 spider species with sex-resolved transcriptomic and chromatin profiling in the highly dimorphic Joro spider, Trichonephila clavata. Across spiders, we identified SSD-associated evolutionary-rate shifts in genes involved in chromatin regulation, growth, and cuticle structural organization. We further found a significant positive association between JHAMT copy number and SSD, with larger gene repertoires occurring in more extremely dimorphic lineages. In T. clavata, expanded JHAMT paralogs showed sex- and tissue-biased expression together with sex-specific differences in chromatin accessibility and local chromatin interactions. Integrated multi-omic analyses further revealed coordinated sex-specific differences in transcription, chromatin accessibility, and chromatin interactions across genes involved in ecdysteroid signaling, insulin and growth regulation, and epidermal and cuticular processes. Altogether, these findings provide insight into the evolutionary and regulatory changes associated with extreme female-biased SSD in spiders.

zoology↗

bioRxiv2026

The function of human PIF1 in G quadruplex formation and replication stress response at ALT telomeres

Cancers maintain their telomeres through two telomere maintenance mechanisms: 85-90% of cancers rely on telomerase (TEL+), while 10-15% of cancers adopt the Alternative Lengthening of Telomeres (ALT) pathway. The Break-Induced Replication (BIR) pathway plays a critical role in maintaining telomere length in the ALT+ cells. In both yeast and human, PIF1, a 5' to 3' helicase, is required for the robust activity of BIR. However, the extent of human PIF1 (hPIF1) involvement in the ALT pathway remains unknown. Here we showed that hPIF1 can be recruited to damaged telomeres in ALT+ cells. In addition, we demonstrated that inhibition of hPIF1 induced DNA damage and G quadruplex (G4) accumulation at ALT telomeres, leading to a moderate reduction of the mean telomere length. Most interestingly, we demonstrated that inhibition of hPIF1 also attenuates checkpoint activation, BLM recruitment, single-stranded DNA (ssDNA) formation, DNA damage, and G4s at telomeres in the FANCM deficient ALT+ cells. Finally, we showed that inactivation of hPIF1 affects the viability of both ALT+ and TEL+ cancers, suggesting that hPIF1 is a potential drug target for cancer therapy.

molecular biology↗

bioRxiv2026

DNMT mRNA stability and YB-1 cooperatively regulate ABCB1 to drive cisplatin chemoresistance in cholangiocarcinoma

Background and AimsIntrahepatic cholangiocarcinoma (iCCA) is a tumor type with a high lethality due to late diagnosis and profound resistance to conventional chemotherapy. To date the molecular mechanisms underlying multidrug resistance remain poorly defined. Here, we integrate single-cell transcriptomics, clinicopathological analysis, and functional genomics to elucidate the molecular basis of cisplatin resistance in iCCA. Approach and ResultsSingle-cell RNA sequencing of iCCA and adjacent liver tissues revealed pronounced expression of Y-box-binding protein 1 (YB-1) in aneuploid malignant cholangiocarcinoma cells, with YB-1 expression progressively increasing during malignant evolution and strongly associated with chemoresistance. Clinically, elevated YB-1 expression-particularly its nuclear localization-robustly predicts poor overall survival and chemotherapy failure in patients with iCCA. Mechanistically, we demonstrate that cisplatin induces phosphorylation-dependent nuclear translocation of YB-1, enabling direct transcriptional activation of the drug efflux transporter ABCB1. Importantly, this process requires ABCB1 promoter demethylation, which is driven by cisplatin-induced, mA-dependent destabilization of DNMT1 and DNMT3B mRNAs. This destabilization occurs through disruption of the YB-1-IGF2BP1/3-DNMT mRNA stabilizing complex and subsequent recruitment of DNMT transcripts to YTHDF2-mediated processing bodies for degradation. ConclusionsOur findings uncover a previously unrecognized YB-1-mA-DNMT regulatory axis that drives chemotherapeutic resistance in iCCA, highlighting YB-1 as both a prognostic biomarker and a promising therapeutic target.

molecular biology↗

bioRxiv2026

Nuclear speckle protein SON safeguards efficient splicing of GC-rich genes

Gene architecture in higher eukaryotes exhibits substantial heterogeneity. While most genes follow a canonical pattern of GC-rich exons and AT-rich introns, a subset displays GC-leveled architecture, characterized by uniformly high GC content across both exons and introns. These genes are often associated with nuclear speckles, membraneless compartments enriched in RNA-processing factors, yet the mechanistic basis of this spatial and functional relationship remains unclear. Here, we identify the nuclear speckle protein SON as a critical factor that safeguards the splicing of GC-rich genes. Acute depletion of SON in mouse embryonic stem cells selectively impairs the splicing of short, GC-rich introns. These SON-dependent introns are enriched in highly expressed and functionally essential genes, whose GC-rich architecture contributes to efficient RNA processing and expression. Mechanistically, these introns harbor atypical C-rich, U-poor polypyrimidine tracts at their 3 splice sites, which exhibit reduced affinity for core splicing factors. SON is recruited to these sites via U2 snRNP and further interacts with SR proteins to stabilize the association of U2 snRNP and U2AFs at these C-rich weak splice sites. Notably, the evolutionary expansion of SONs intrinsically disordered region is required to promote efficient splicing of GC-rich genes that emerged during evolution. Together, our study suggests that the evolutionary transition toward GC-rich gene architecture enhances gene expression efficiency, with SON acting to safeguard the splicing of this gene class.

molecular biology↗

bioRxiv2025

Introduction, spread, and evolutionary dynamics of non-native spiders in North America

Tracing the introduction, spread, and evolution of non-native species is crucial for risk assessment and management. Spiders represent one of the largest groups of terrestrial arthropod predators, and an increasing number of species have been introduced globally, posing growing challenges to local biodiversity and ecosystem stability. Yet, their global introduction routes, spatial diversity patterns, and evolutionary dynamics remain poorly understood. Here, we conducted a global-scale survey of 53,172 taxon records and updated the checklist of North American spiders to 5,401 species, including 118 non-native species. By integrating historical records with species occurrence data, we reconstructed the geographic origins of non-native species and found that most originated from Asia and Europe, consistent with long-standing transcontinental trade and intensive human activities. Mapping the contemporary distributions of all non-native species revealed at least six richness hotspots, such as Los Angeles and San Francisco metropolitan areas, underscoring strong associations between non-native spider accumulation and population density, trade intensity, and human-mediated dispersal pathways. By analyzing genomes of 45 native and five non-native spider species within North America, we detected a set of metabolic, stress tolerance and immune defense genes under positive selection and rapid evolution in non-native species, suggesting that putative functional innovations may contribute to their establishment, expansion, and ongoing local adaptation. Altogether, our study provides the most comprehensive survey to date of introduction routes, spatial dynamics, and evolutionary signatures of non-native spiders in North America, and highlights putative mechanisms that may facilitate arthropod introductions under global change.

ecology↗

bioRxiv2025

Genomic signature of repeated transitions to diurnality in spiders

Repeated transitions to diurnality represent a major behavioral shift in spiders, yet their genomic underpinnings remain largely unknown. Here, we assembled high-quality genomes for nine diurnal spiders using long-read sequencing and compiled diel activity phenotypic data through a combination of meta-analysis and field assessments. By integrating all publicly available spider genomes, we examined the genomic evolutionary dynamics of 67 species including at least 5 independent origins of diurnality. Across diurnal spider lineages, hundreds of genes exhibited convergent shifts in selection, including intensified selection on neural, locomotion, and visual system genes, and relaxed selection on several core phototransduction components. Notably, diurnal spiders showed convergent deceleration in evolutionary rates in circadian regulators, such as CLOCK and CRTC1, and they harbored distinct repertoires of positively selected genes relative to non-diurnal species. In addition, convergent amino acid substitutions were enriched in diurnal hunting spiders. Comparative multi-tissue transcriptomics showed that genes under convergent selection, particularly those involved in vision, sensory processing, nervous system development, and locomotion, tended to exhibit stronger eye- and brain-biased tissue specificity in diurnal species. Altogether, our results reveal convergent genomic changes associated with repeated evolution of diurnality and illustrate how ecological light environments repeatedly shape the molecular evolution of complex animal behavior.

evolutionary biology↗

bioRxiv2025

Genomic signatures associated with convergent funnel-web building behavior in spiders

Spiders exhibited diverse and intricate web-building behaviors, which represent a classic model for studying the evolution of complex traits. The funnel-web, a sheet-like web with a retreat tube, has evolved independently in several spider lineages, especially in the families Agelenidae and Macrothelidae. This repeated emergence of a complex behavior offers an example of this funnel-web building behavioral convergence. Here, we present a chromosome-level genome assembly of the agelenid spider Tamgrinia laticeps, along with annotated genomes of another agelenid spider Eratigena atrica, and a macrothelid Orientothele yani which convergently evolved funnel-web building behavior. Comparative genomic analysis of 15 spider species with diverse web-types revealed convergent signatures associated with funnel-web construction. Hundreds of genes tended to experience convergent shift in selective pressure, convergent positive section, and harbored convergent amino acid substitutions. These genes are associated with synaptic transmission (e.g., SLC6A3, Gabbr1, SNAP25), neuromuscular coordination (e.g., ine, VAChT), and behavioral regulation (e.g., Crtc1, Lrrc7). Notably, we detected identical convergent amino acid changes in VAChT and ine across all three funnel-web builders. Our findings demonstrate that convergent evolution of web architecture is linked to nervous system evolution, providing genomic insights into the basis of behavioral convergence.

genomics↗

bioRxiv2025

The anti-phage mechanism of a widespread trypsin-MBL module

Protease mediate activation of immune effectors is a conserved mechanism across life. This study identified a widespread and co-evolving trypsin-MBL module as a core effector in diverse bacterial immune systems (e.g., Hachiman, Argonaute, AVAST), protecting host via abortive infection. Focusing on Hachiman-trypsin-MBL, we demonstrated that, the protease activity of trypsin*HamAB is inhibited in the presence of ATP and MBL is an autoinhibited DNase with two inserted loops blocking the catalytic pocket. Upon infection, the HamB helicase senses invading nucleic acids and catalyzes the hydrolysis of ATP, activating the associated trypsin-like protease that cleaves specifically at two non-canonical KSS motif of MBL and releases its DNase activity. Cryo-EM structures of activated trypsin*HamAB bound with DNA reveal DNA binding and ATP hydrolysis lead to the release of the trypsin-like domain, enabling activation. Our work provides a comprehensive understanding on the mechanism of widely distributed trypsin-MBL module, wherein proteolytic activation of a toxic nuclease enables robust bacterial immunity while preventing self-toxicity through multi-layered control.

biochemistry↗

bioRxiv2025

Genomics of eye number evolution in spiders

Spiders exhibit tremendous variations in eye numbers, but the genomic basis underlying this diversity remains largely unexplored. Here, we analyzed the genomic data of 148 spider species in 31 families, representing all phenotypes of eye numbers including 8, 6, 4, 2, and 0. Our analyses revealed that a core set of 29 genes involved in eye development and phototransduction is conserved across all spiders, irrespective of their eye number, indicating that eye reduction is not caused by the loss of key developmental genes. We found that evolutionary transitions leading to reduced numbers of eyes are primarily associated with parallel genome-wide relaxed selection. While these independent reduction events shared several genes under consistent selective pressures, they did not share any genes under positive selection, indicating putatively divergent molecular mechanisms. In contrast, the evolution of complete eye loss in cave-dwelling spiders is associated with parallel genome-wide intensified selection. Notably, we identified shared genes under both intensified and positive selection across independent origins of eyelessness, suggesting a parallel molecular mechanism. Altogether, our study provides genomic insights into the parallel evolution of eye reduction and complete eye loss in spiders.

evolutionary biology↗

bioRxiv2025

Regulation of essential hepatocyte functions and identity by super-enhancers in health and disease

Physiologically, hepatocytes perform an estimated 500 essential liver functions to ensure systemic homeostasis. The mechanisms how hepatocytes maintain these numerous crucial functions in response to physiological and pathophysiological challenges are largely unknown. In this study, we found that vital liver function genes (e.g., HNF4A, ALB, coagulation factors, and SLC2A2) in hepatocytes possess super-enhancers. Interfering with the super-enhancers by dCas9-sgRNA remarkably decreases the expression of these genes. Quiescent liver progenitor cells (LPCs) do not have active super-enhancers in vital liver function genes. In acute liver failure (ALF) caused by massive hepatic necrosis, activated LPCs perform liver function and differentiate into hepatocytes to rescue patients lives. We show that activated LPCs gradually form super-enhancers in liver function genes (e.g., HNF4A, ALB, and coagulation factors) during proliferation and differentiation. These super-enhancers are regulated by FOXA2 through the recruitment of HNF4 a, p300 and Mediators in most liver function genes, such as ALB and coagulation factors. However, super-enhancers in some genes (e.g., SLC2A2) are FOXA2-indenpendent. Hepatic FOXA2 expression is closely associated with the clinical outcome of ALF. In a cohort of ALF patients, robust FOXA2 is observed only in the surviving patients. Collectively, super-enhancers represent a critical epigenetic regulatory mechanism that enables rapidly enhanced transcription of liver function genes in response to pathophysiological challenges. In urgent clinical syndrome such as ALF, LPCs rescue liver function by rapid formation of super-enhancers in vital genes.

molecular biology↗

bioRxiv2025

TGF-β serves as a critical signaling determinant of liver progenitor cell fate and function

Liver progenitor cells (LPCs) are the smallest cholangiocytes that perform hepatocyte functions to rescue the lives of patients suffering from acute liver failure (ALF) caused by massive hepatic necrosis (MHN). To date, it remains largely unknown how LPCs remain quiescent and become activated following MHN. This study elucidates the essential role of TGF-{beta} in regulating LPC quiescence and activation. Spatial transcriptomics analysis of liver tissues from four MHN-ALF patients revealed that LPCs receive multiple active signals from surrounding macrophages and hepatic stellate cells, including TGF-{beta}, HGF, and EGF. Physiologically, TGF-{beta} inhibits LPC proliferation by impeding G1-S phase transition. Ectopic Smad7 expression remarkably increased LPC proliferation in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-fed mice. Intriguingly, extensive LPC proliferation was observed in ALF patients despite robust TGF-{beta}-p-SMAD2 signaling in activated LPCs. Immunohistochemistry and immunofluorescence revealed significantly elevated expression of p-MET, p-STAT3, p-EGFR, and p-ERK in LPCs, indicating active HGF and EGF signaling. In vitro, either HGF or EGF promoted LPC proliferation despite the presence of TGF-{beta}. Beyond acting as mitogens, HGF and EGF regulate master hepatocyte genes (e.g., HNF4) and cholangiocyte genes (e.g., SOX9) in LPCs. Notably, HGF-dependent HNF4 required TGF-{beta}-activated SMADs. Collectively, TGF-{beta} serves as a critical signaling determinant of LPC fate and function.

cell biology↗

bioRxiv2025

Metabolic and transcriptomic insights into a GalNAc/Man-Specific lectin in yeast fermentation

Brewers yeast (Saccharomyces cerevisiae) plays a central role in fermentation, and improving its performance is crucial in the brewing industry. This study explored how Cyclina sinensis lectin (CSL), a bioactive peptide from shellfish, influences yeast metabolism using proteomics and metabolomics. CSL bound to yeast peptidoglycan in a concentration-dependent manner and altered cell surface structure. Proteomic analysis revealed 117 differentially expressed proteins after 24 h of CSL treatment, with upregulation of key glycolytic enzymes (e.g., hexokinase, GAPDH) and downregulation of TCA cycle enzymes, suggesting enhanced ethanol production via glycolysis activation and TCA suppression. Metabolomic profiling further confirmed this, showing increased -D-glucose, glucose-6-phosphate, NAD+, and glutathione, alongside reduced TCA intermediates like malic acid. These results indicate CSL promotes ethanol accumulation by reprogramming central carbon metabolism. This study provides novel insight into the metabolic modulation of yeast by marine lectins and suggests potential applications of CSL in improving fermentation

microbiology↗

bioRxiv2025

MF-PENS: An Efficient and Versatile Nuclear Extraction Method for Plant Single-Cell Sequencing

The widespread adoption of single-cell transcriptomics in plants remains constrained by the challenges of isolating high-quality nuclei from tissues with rigid cell walls and complex metabolomes. Here, we present methanol fixation and Percoll-enriched nuclei sorting (MF-PENS), a robust strategy designed to tackle these limitations. Distinct from conventional protocols, MF-PENS circumvents the need for fluorescence activated cell sorting (FACS) and effectively reduce RNA leakage, consistently yielding high-quality single-nucleus RNA sequencing (snRNA-seq) data. MF-PENS has been validated across various plant tissues, including fresh and frozen rice roots and leaves, as well as recalcitrant samples such as soybean root nodules, soybean seeds, and tomato fruits. Benchmarking results demonstrate that MF-PENS significantly enhances gene capture efficiency, cell clustering performance, and cell type annotation accuracy. With its broad applicability and superior performance, MF-PENS represents a robust and versatile tool for plant single-cell research, facilitating deeper insights into plant development and biology processes.

plant biology↗

bioRxiv2025

A monophyletic origin of domesticated barley

The origin of domesticated barley has been debated extensively over the past century. Early botanical and comparative morphological research and recent genetic research supported a polyphyletic origin. A monophyletic origin was proposed after the discovery that a single genetic locus controls the presence of hull-less grains in all domesticated barley. Interpreting the origin of domesticated barley is further complicated by the archaeological record showing that the first domesticates had two rows of grain on the inflorescence, as does its wild progenitor. However, these two-rowed types effectively disappeared from the record for thousands of years, and they were replaced by derived six-rowed types that dominated barleys cultivation history and only reappeared in the record around one thousand years ago. Here, we used two independent datasets with large sample sizes and genome-wide genetic markers to re-evaluate barley cultivation history. We unequivocally demonstrate that modern domesticated barley has a monophyletic origin. Phylogenetic reconstruction and examination of current archaeological records suggests that the west Fertile Crescent was most likely where barley was first domesticated. Modern two-rowed types were likely derived from six-rowed domesticated types not earlier than 3,500 years ago in modern Turkiye and Iran. We conclude that the two distinct non-brittle rachis haplotypes, coinciding with distinct row types in cultivated barley, are likely the results of two chronological events along the same evolutionary line. Our results provide a reconcilable framework for explaining genetic and phytogeographic patterns and pave the way for a consensus on the origin of barley domestication.

evolutionary biology↗

bioRxiv2024

Cerebral Blood Volume Modulates Glymphatic Influx Through Extra-ventricular Cerebrospinal Fluid Volume

The glymphatic system facilitates waste removal via cerebrospinal fluid (CSF) influx alongside perivascular spaces throughout the brain. Vasomotion, the slow motion of blood vessel (0.1-0.3 Hz), has been found to be one of the driving forces for perivascular clearance, but it is not clear whether more chronical change of vessel diameter, as reflected by macroscopic cerebral blood volume (CBV), has any impact on glymphatic function. Combining multimodal mouse MRI techniques, we investigated the relationship among glymphatic influx, CBV, CSF volume and EEG power under six different conditions (awake, dexmedetomidine, isoflurane, isoflurane/dexmedetomidine, ketamine/xylazine and awake with caffeine). We found dexmedetomidine and caffeine enhanced glymphatic influx, while isoflurane reduced it compared with awake condition. Quantitative CBV imaging revealed that glymphatic influx was negatively correlated to CBV across the above conditions. Furthermore, such negative correlation was found to be mediated in part by changes of extra-ventricular CSF volume, which was quantified using T1 MRI. Taken together, our results suggest that CBV is a consciousness independent modulator of glymphatic function and modulates glymphatic influx through extra-ventricular CSF volume. This new finding opens potential avenues to enhance brain waste clearance by regulating CBV, which could be beneficial for protein deposition related neurological diseases. TeaserCBV is a consciousness independent modulator of glymphatic function and modulates glymphatic influx through extra-ventricular CSF volume.

neuroscience↗

bioRxiv2024

Relaxed selection and horizontal gene transfer fuel underwater adaptation in a water spider

Spiders have primarily adapted to terrestrial life, yet a number of species have made evolutionary transitions to marine and freshwater environments. While its physiological and behavioral adaptations have been characterized, the genetic basis of semi-aquatic and aquatic adaptation in spiders remains poorly understood. Here, we provide a high-quality, chromosome-level genome assembly for the aquatic spider Argyroneta aquatica, alongside a reference transcriptome for the semi-aquatic spider Desis martensi. We performed comparative genomes analyses of 22 spider species, including a unique aquatic spider, two semi-aquatic spiders and 19 terrestrial spider species, with a focus on those in the marronoid clade. By integrating morphological, phylogenomic, comparative genomic, transcriptomic, and metabolomic analyses, we explored the genomic adaptations of aquatic and semi-aquatic spiders. Phylogenomic analysis suggests that aquatic and semi-aquatic spiders have independently evolved from their terrestrial ancestors and represent divergent evolutionary routes We found hundreds of genes tend to experience relaxed selection, positive selection, and evidence of horizontal gene transfer (HGT) associated with the transition to aquatic and semi-aquatic life in spiders. These genes are associated with respiratory, osmoregulatory, fat metabolism and digestion, hypoxia, and thermal functions, putatively facilitate the adaptations to diverse underwater life. Altogether, our findings highlight the divergent evolutionary mechanisms enabling spiders to thrive in diverse aquatic environments, providing insights into the genomic basis of adaptations to semi-aquatic and aquatic habitats.

genomics↗

bioRxiv2023

Population genomic analysis reveals high inbreeding in a Hawksbill turtle population nesting in Singapore

Seven species of marine turtles remain in a world currently threatened by anthropogenic activities and climate change, standing at the precipice of extinction. Urgent conservation endeavours are imperative to safeguard their survival and preserve the biodiversity of marine ecosystems. Yet, genetic studies on these turtles have leaned on restricted genetic markers, such as the mitochondrial control region. The markers could provide incomplete or biased estimations of genetic diversity and population structure, thereby limiting precise conservation strategies. Here, we have generated a de novo genome assembly and high-quality whole-genome population datasets from hawksbill turtles nesting and foraging in Singapore. This initiative aims to contribute to unbiased, fine-resolution genetic data on the species, conducting a comprehensive population genomic study. Our analysis results demonstrated a remarkable enhancement in genetic markers. While we identified five different haplotypes defined by five variants within 69 mitochondrial control region sequences, the analysis of 35 whole genome sequences uncovered approximately 12 million single nucleotide polymorphisms (SNPs). Within the Singapore hawksbill turtle population, our whole-genome analysis revealed a pronounced degree of inbreeding, with most samples sharing at least a first cousin relationship. Furthermore, within a multiple-paternity nest, we identified related parents. Additionally, our inference of demographic history underscored the impact of past climate change on the decreasing hawksbill turtle population. We believe this pioneering study will substantially enhance the field of conservation genetic study of marine turtles.

genomics↗

bioRxiv2023

FOXA2 is essential for maintaining the urea cycle in acute liver failure

Hepatic encephalopathy is a lethal complication of acute liver failure (ALF), and is caused by hyperammonemia. Ammonia clearance by the liver requires an intact and complete urea cycle comprising six enzymes, including the rate-limiting enzyme carbamoyl phosphate synthetase I (CPS1). To date, the detailed regulation of CPS1 transcription in order to maintain urea cycle in physiological condition and ALF remains largely unknown. This study scrutinizes the role of pioneer factor forkhead box A 2 (FOXA2) in the regulation of CPS1 transcription, urea cycle performance and hyperammonemia. Physiologically, CPS1 transcription requires FOXA2 to maintain chromatin accessibility on its enhancers, which is essential for CCAAT enhancer-binding protein-alpha (C/EBP) binding to activate gene transcription. In ALF, hepatic C/EBP expression is inhibited by inflammatory mediators such as TGF-{beta} and TNF-. In this setting, retinoic acid receptor synergizes with FOXA2 to maintain CPS1 transcriptions. Once ALF patients suffer from massive hepatic necrosis, liver progenitor cells initiate a transcription network comprising FOXA2 and C/EBP to perform the urea cycle and prevent hyperammonemia. In ALF, hepatic encephalopathy occurs in patients lacking hepatic FOXA2 expression. In mice with acetaminophen-induced ALF, injection of Foxa2-AAV8 maintains urea cycle and prevents hyperammonemia. Taken together, FOXA2 is essential for maintaining the urea cycle. Pharmaceutical induction of hepatic FOXA2 expression might represent a novel approach to treat hepatic encephalopathy in ALF. One Sentence SummaryPioneer factor FOXA2 synergizes with C/EBP or RAR to maintain urea cycle in acute liver failure

molecular biology↗