Biology subjects

Diao, S.

Publications and source records attributed to Diao, S..

6 recordsLinked to original sources

bioRxiv2024

Long-term disruption of glucose homeostasis in a rodent model of preterm birth.

Around 1 of every 10 babies is born preterm, and the incidence of preterm birth has been rising. The long-term consequences of preterm survivors are not fully understood. Preterm birth is proven to be associated with metabolic diseases and related disorders later in life. Preterm newborns are susceptible to perinatal inflammatory events such as chorioamnionitis, hypoxia-ischemia, and sepsis. We hypothesized that perinatal inflammation has a role in the developmental programming of metabolic diseases and related disorders. In the present study, perinatal inflammation was modeled by systemic administration of IL-1{beta} in mice. We observed a pronounced sexual dimorphism where only the males presented significant insulin resistance and glucose intolerance accompanied by leptin resistance in the long term following perinatal inflammation exposure. Adiposity and energy homeostasis were intact. It showed that perinatal inflammation selectively contributes to the long-term dysregulation of glucose metabolism in a sex-dependent manner. The underlying mechanism might be linked with hypothalamic inflammation and upregulated circulating CCL5. Metformin treatment might be optional to treat insulin resistance resulting from perinatal inflammation. HighlightsO_LIPerinatal inflammation is common in preterm infants, often leading to perinatal brain injuries. However, the long-term metabolic outcomes of these infants are not fully revealed. C_LIO_LIWe explored the long-term metabolic outcomes in mice with perinatal IL-1{beta} exposure and sought its association with inflammation. C_LIO_LIPerinatal inflammation has a profound and deleterious role in glucose metabolism in a sex-dependent and time-dependent manner. C_LIO_LIPerinatal inflammation might be a risk factor for metabolic disorders in preterm survivors. C_LI

physiology↗

bioRxiv2023

C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity

Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis (Dammann, O. and Leviton, A., Intermittent or sustained systemic inflammation and the preterm brain. Pediatr Res, 2014. 75(3): p. 376-80). In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery (Luca, A.,et al., Birth trauma in preterm spontaneous vaginal and cesarean section deliveries: A 10-years retrospective study. PloS one,2022, 17(10), e0275726.) We have developed and characterized a mouse model based on intraperitoneal injections of IL-1{beta} between postnatal days one and five to reproduce perinatal systemic inflammation (Favrais, G.,et al., Systemic inflammation disrupts the developmental program of white matter. Ann Neurol,2011. 70(4): p. 550-65). This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1{beta} on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders. Significance StatementIn a well-established mouse model of the encephalopathy of prematurity, we observed that C-section exacerbates the deleterious effects of neonatal systemic inflammation (intraperitoneal injections of IL-1{beta} between postnatal days one and five) on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced brain functional connectivity. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.

neuroscience↗

bioRxiv2023

Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of complex traits in pig.

Understanding the molecular and cellular mechanisms that underlie complex traits in pigs is crucial for enhancing their genetic improvement program and unleashing their substantial potentials in human biomedicine research. Here, we conducted a meta-GWAS analysis for 232 complex traits with 28.3 million imputed whole-genome sequence variants in 70,328 individuals from 14 pig breeds. We identified a total of 6,878 genomic regions associated with 139 complex traits. By integrating with the Pig Genotype-Tissue Expression (PigGTEx) resource, we systemically explored the biological context and regulatory circuits through which these trait-associated variants act and finally prioritized 16,664 variant-gene-tissue-trait circuits. For instance, rs344053754 regulates the expression of UGT2B31 in the liver by affecting the activity of regulatory elements and ultimately influences litter weight at weaning. Furthermore, we investigated the conservation of genetic and regulatory mechanisms underlying 136 human traits and 232 pig traits. Overall, our multi-breed meta-GWAS in pigs provides invaluable resources and novel insights for understanding the regulatory and evolutionary mechanisms of complex traits in both pigs and humans.

genetics↗

bioRxiv2023

The ChickenGTEx pilot analysis: a reference of regulatory variants across 28 chicken tissues

Chicken is a valuable model for understanding fundamental biology, vertebrate evolution and diseases, as well as a major source of nutrient-dense and lean-protein-enriched food globally. Although it is the first non-mammalian amniote genome to be sequenced, the chicken genome still lacks a systematic characterization of functional impacts of genetic variants. Here, through integrating 7,015 RNA-Seq and 2,869 whole-genome sequence data, the Chicken Genotype- Tissue Expression (ChickenGTEx) project presents the pilot reference of regulatory variants in 28 chicken tissue transcriptomes, including millions of regulatory effects on primary expression (including protein-coding genes, lncRNA and exon) and post-transcriptional modifications (alternative splicing and 3 untranslated region alternative polyadenylation). We explored the tissue-sharing and context-specificity of these regulatory variants, their underlying molecular mechanisms of action, and their utility in interpreting adaptation and genome-wide associations of 108 chicken complex traits. Finally, we illustrated shared and lineage-specific features of gene regulation between chickens and mammals, and demonstrated how the ChickenGTEx resource can further assist with translating genetic findings across species. One-Sentence SummaryThe ChickenGTEx provides a multi-tissue reference of regulatory variants for chicken genetics and genomics, functional genomics, precision breeding, veterinary medicine, vertebrate evolution and even human biomedicine.

genetics↗

bioRxiv2022

A compendium of genetic regulatory effects across pig tissues

The Farm animal Genotype-Tissue Expression (FarmGTEx, https://www.farmgtex.org/) project has been established to develop a comprehensive public resource of genetic regulatory variants in domestic animal species, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biology discovery and exploitation in animal breeding and human biomedicine. Here we present results from the pilot phase of PigGTEx (http://piggtex.farmgtex.org/), where we processed 9,530 RNA-sequencing and 1,602 whole-genome sequencing samples from pigs. We build a pig genotype imputation panel, characterize the transcriptional landscape across over 100 tissues, and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We study interactions between genotype and breed/cell type, evaluate tissue specificity of regulatory effects, and elucidate the molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying about 80% of the genetic associations for 207 pig complex phenotypes, and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, corroborating the importance of pigs as a human biomedical model.

genomics↗

bioRxiv2022

Molecular and genetic mechanisms conferring dissolution of dioecy in Diospyros oleifera Cheng

Dioecy, a sexual system of single-sex (gynoecious/androecious) individuals, is rare in flowering plants. This rarity may be a result of the frequent transition from dioecy into systems with co-sex individuals. Here, we report potential molecular and genetic mechanisms that underlie the dissolution of dioecy to monoecy and andro(gyno)monoecy, based on multiscale genome-wide investigations of 150 accessions of Diospyros oleifera. All co-sex D. oleifera plants, including monoecious and andro(gyno)monoecious individuals, possessed the male determinant gene OGI, implying that genetic factors control gynoecia development in genetically male D. oleifera. In both single- and co-sex plants, female function was expressed in the presence of a genome-wide decrease in methylation levels, along with sexually distinct regulatory networks of smRNAs and their targets. Furthermore, a genome-wide association study (GWAS) identified a genomic region and a DUF247 gene cluster strongly associated with the monoecious phenotype, as well as several regions that may contribute to andromonoecy. Collectively, our findings imply stable breakdown of the dioecious system in D. oleifera, presumably a result of the genomic features of the sex-linked region.

plant biology↗