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Yu Guo

Publications and source records attributed to Yu Guo.

6 recordsLinked to original sources
PubMed2026

A horizontally acquired gene mediates insect cocoon pigmentation in the eri silkmoth, Samia ricini.

Holometabolous insects make cocoons during larval-pupal metamorphosis to protect the pupal phase. The materials used for cocoon construction vary widely. Lepidopteran insects typically secrete silk to form cocoons, which display diverse colors. The eri silkworm, Samia cynthia ricini, is an economically important domesticated species that mostly produces white cocoons, with some varieties producing red cocoons. The enzyme kynureninase (KYNU), acquired from bacteria by horizontal gene transfer, has previously been implicated in insect coloration, while the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) has been identified as a red pigment. However, exactly how KYNU is involved in cocoon pigmentation remains unclear. Here, we report that a horizontally transferred bacterial gene encoding KYNU regulates red cocoon formation. Metabolomic analysis revealed a high accumulation of 3-HAA in red cocoons, confirming its role as the primary pigment and associating the coloration with tryptophan metabolism. Quantitative real-time polymerase chain reaction (qPCR) analysis indicated that SrKYNU is highly expressed in the silk glands and significantly downregulated in the red cocoon strain compared to the white cocoon strain. Genomic sequencing identified a 141 bp deletion in the upstream regulatory region of KYNU in the red cocoon strain compared to the white cocoon strain. Dual-luciferase assays confirmed that this deletion significantly reduced promoter activity. CRISPR/Cas9 knockout of SrKYNU in the white-cocoon strain resulted in mutants producing red cocoons with elevated 3-HAA content. These findings reveal that the horizontally transferred gene SrKYNU exhibits tissue-specific expression and regulates cocoon coloration in S. ricini, illustrating that horizontal gene transfer can play an important role in regulating an insect physiological process.

Animals↗
PubMed2026

IGF2BP1-Mediated m⁶A Modification Stabilizes HMGA2 mRNA to Promote Intrahepatic Cholangiocarcinoma Progression.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) remains a lethal malignancy with a lack of effective therapies, underscoring the critical need to identify novel therapeutic targets. The high-mobility group protein A2 (HMGA2) is an oncogenic architectural transcription factor aberrantly overexpressed in multiple cancers; yet its function and regulatory mechanisms in iCCA are poorly defined. This study aimed to elucidate the clinical significance and molecular mechanism of HMGA2 in iCCA progression. METHODS: We integrated analyses across 4 independent iCCA cohorts (The Cancer Genome Atlas, 2 Zhongshan Hospital cohorts, and our 192-patient institutional cohort). Functional investigations were conducted using iCCA cell lines and multiple mouse models, including xenograft, syngeneic, YAP/AKT-driven spontaneous iCCA, and metastasis models. RESULTS: We demonstrated that HMGA2 was significantly upregulated in iCCA, correlating with poor survival, and exhibited sexually dimorphic prognostic effects with a female-specific link to perineural invasion. Functionally, HMGA2 depletion suppressed iCCA cell proliferation, migration, in vivo tumor growth and metastasis. Mechanistically, HMGA2 expression was positively regulated by the N6-methyladenosine reader insulin-like growth factor 2 messenger RNA-binding protein 1 (IGF2BP1), which directly bound to and stabilized HMGA2 messenger RNA via its KH3-4 domains in an N6-methyladenosine-dependent manner. High IGF2BP1 expression predicted poor iCCA prognosis, was required for HMGA2-driven progression, and the axis promoted PI3K-AKT pathway activation. CONCLUSIONS: Our results reveal a critical role for the IGF2BP1-HMGA2 axis in iCCA pathogenesis, thereby highlighting its potential as a therapeutic target.

Cholangiocarcinoma↗
PubMed2026

Chronic heart failure and GPX3 promoter methylation: A clinical-epigenetic analysis.

BACKGROUND: Selenoprotein GPX3 is linked to Chronic Heart Failure (CHF), but its promoter methylation patterns in CHF remain unclear. OBJECTIVE: To explore CpG methylation in the GPX3 promoter region and its association with clinical parameters in CHF. METHODS: Twenty CHF patients and twenty healthy controls were included. Methylation levels of CpG sites within the GPX3_FA28 promoter region were quantified. Group differences were assessed using appropriate statistical tests. Restricted cubic spline (RCS) models were applied to explore dose-response associations between differentially methylated CpG sites and clinical indicators across multiple physiological systems. RESULTS: Significant locus-specific methylation alterations were identified in CHF patients. CpG_5 showed hypermethylation (P = 0.017), while CpG_9 (P = 0.045) and CpG_19 (P = 0.008) were hypomethylated compared with controls. Patients with NYHA class I/II exhibited higher methylation at CpG_1 (P = 0.028) and CpG_2 (P = 0.040). CpG_5 methylation displayed nonlinear associations (P < 0.05) with total bilirubin (inverted U-shape), carbon dioxide (triphasic), total cholesterol (U-shape), and plateletcrit (wave-like). CpG_9 correlated with activated partial thromboplastin time and hematopoietic markers, while CpG_19 was linked to eosinophil percentage and erythrocyte parameters. CONCLUSIONS: GPX3 promoter methylation displays apparent locus specificity in CHF. Different CpG sites may contribute to CHF pathophysiology through distinct epigenetic mechanisms. These findings highlight the potential of GPX3 methylation as a stratified biomarker in CHF.

Humans↗
PubMed2025

On the origin of the late-flowering ppd-H1 allele in barley.

To breed for climate resilient crops, an understanding of the genetic and environmental factors influencing adaptation is critical. Barley provides a model species to study adaptation to climate change. Here we present a detailed analysis of genetic variation at a major photoperiod response locus and relate this to the domestication history and dispersal of barley. The PPD-H1 locus (a PSEUDO-RESPONSE REGULATOR 7) promotes flowering under long-day conditions, and a natural mutation at this locus resulted in a recessive, late-flowering ppd-H1 allele. This mutation proved beneficial in high-latitude environments such as Northern Europe, where it allows extended vegetative growth during long spring days. We infer the origin of the mutated late-flowering ppd-H1 allele by re-sequencing a large geo-referenced collection of 942 Hordeum spontaneum, 5 Hordeum agriocrithon and 1110 domesticated (Hordeum vulgare) barleys. We demonstrate that the late-flowering phenotype originated from Desert-type wild barley in the Southern Levant and present evidence suggesting a post-domestication origin of the mutated ppd-H1 allele.

Hordeum↗
PubMed2025

A haplotype-resolved pangenome of the barley wild relative Hordeum bulbosum.

Wild plants can contribute valuable genes to their domesticated relatives1. Fertility barriers and a lack of genomic resources have hindered the effective use of crop-wild introgressions. Decades of research into barley's closest wild relative, Hordeum bulbosum, a grass native to the Mediterranean basin and Western Asia, have yet to manifest themselves in the release of a cultivar bearing alien genes2. Here we construct a pangenome of bulbous barley comprising 10 phased genome sequence assemblies amounting to 32 distinct haplotypes. Autotetraploid cytotypes, among which the donors of resistance-conferring introgressions are found, arose at least twice, and are connected among each other and to diploid forms through gene flow. The differential amplification of transposable elements after barley and H.&#x2009;bulbosum diverged from each other is responsible for genome size differences between them. We illustrate the translational value of our resource by mapping non-host resistance to a viral pathogen to a structurally diverse multigene cluster that has been implicated in diverse immune responses in wheat and barley.

Hordeum↗
PubMed2022

Temporal associations between leukocytes DNA methylation and blood lipids: a longitudinal study.

BACKGROUND: The associations between blood lipids and DNA methylation have been investigated in epigenome-wide association studies mainly among European ancestry populations. Several studies have explored the direction of the association using cross-sectional data, while evidence of longitudinal data is still lacking. RESULTS: We tested the associations between peripheral blood leukocytes DNA methylation and four lipid measures from Illumina 450&#xa0;K or EPIC arrays in 1084 participants from the Chinese National Twin Registry and replicated the result in 988 participants from the China Kadoorie Biobank. A total of 23 associations of 19 CpG sites were identified, with 4 CpG sites located in or adjacent to 3 genes (TMEM49, SNX5/SNORD17 and CCDC7) being novel. Among the validated associations, we conducted a cross-lagged analysis to explore the temporal sequence and found temporal associations of methylation levels of 2 CpG sites with triglyceride and 2 CpG sites with high-density lipoprotein-cholesterol (HDL-C) in all twins. In addition, methylation levels of cg11024682 located in SREBF1 at baseline were temporally associated with triglyceride at follow-up in only monozygotic twins. We then performed a mediation analysis with the longitudinal data and the result showed that the association between body mass index and HDL-C was partially mediated by the methylation level of cg06500161 (ABCG1), with a mediation proportion of 10.1%. CONCLUSIONS: Our study indicated that the DNA methylation levels of ABCG1, AKAP1 and SREBF1 may be involved in lipid metabolism and provided evidence for elucidating the regulatory mechanism of lipid homeostasis.

Humans↗