Biology subjects

Teng, J.

Publications and source records attributed to Teng, J..

30 records · Page 2Linked to original sources

bioRxiv2023

Construction of a multi-tissue cell atlas reveals cell-type-specific regulation of molecular and complex phenotypes in pigs

The systematic characterization of cellular heterogeneity among tissues and cell-type-specific regulation underlying complex phenotypes remains elusive in pigs. Within the Pig Genotype-Tissue Expression (PigGTEx) project, we present a single-cell transcriptome atlas of adult pigs encompassing 229,268 high-quality nuclei from 19 tissues, annotated to 67 major cell types. Besides cellular heterogeneity within and across tissues, we further characterize prominent tissue-specific features and functions of muscle, epithelial, and immune cells. Through deconvoluting 3,921 bulk RNA-seq samples from 17 matching tissues, we dissect thousands of genetic variants with cell-type interaction effects on gene expression (ieQTL). By colocalizing these ieQTL with variants associated with 268 complex traits, we provide new insights into the cellular mechanisms behind these traits. Moreover, we highlight that orthologous genes with cell-type-specific regulation in pigs exhibit significant heritability enrichment for some human complex phenotypes. Altogether, our work provides a valuable resource and highlights novel insights in cellular regulation of complex traits for accelerating pig precision breeding and human biomedical research.

genetics↗

bioRxiv2023

FarmGTEx TWAS-server: an interactive web server for customized TWAS analysis in both human and farm animals

Transcriptome-wide association study (TWAS) is a powerful strategy for elucidating the molecular mechanisms behind the genetic loci of complex phenotypes. However, TWAS analysis is still daunting in many species due to the complication of the TWAS analysis pipeline, including the construction of the gene expression reference panel, gene expression prediction, and the subsequent association analysis in the large cohorts of genome-wide association study (GWAS). Farm animals are major protein sources and biomedical models for humans. To facilitate the translation of genetic findings across species, here we provide an interactive and easy-to-use multi-species TWAS web server for the entire community, called the FarmGTEx TWAS-server (http://twas.farmgtex.org), which is based on the GTEx and FarmGTEx projects. It includes gene expression data from 49, 34, and 23 tissues in 838 humans, 5,457 pigs, and 4,889 cattle, representing 38,180, 21,037, and 17,942 distinct eGenes in prediction models for humans, pigs, and cattle, respectively. It allows users to conduct gene expression prediction for any individuals with genotypes, GWAS summary statistics imputation, customized TWAS, and popular downstream functional annotation. It also provides 479,203, 1,208, and 657 tissue-gene-trait association trios for the research community, representing 1,129 human traits, 41 cattle traits, and 11 pig traits. In summary, the FarmGTEx TWAS-server is a one-stop solution for performing TWAS analysis for researchers without programming skills in both human and farm animal research communities. It will be maintained and updated timely within the FarmGTEx project to facilitate gene mapping and phenotype prediction within and across species.

bioinformatics↗

bioRxiv2023

Learning functional conservation between pig and human to decipher evolutionary mechanisms underlying gene expression and complex trait

The assessment of genomic conservation between human and pig at the functional level can help understand and improve the potential of pig as a human biomedical model. To address this, we developed a Deep learning-based approach to learn the Genomic Conservation at the Functional level (DeepGCF) between species by integrating 386 and 374 epigenome and transcriptome profiles from human and pig, respectively. DeepGCF demonstrated a better prediction performance compared to the previous functional conservation prediction method. In addition, we showed that the resulting DeepGCF score captures the functional conservation by examining DeepGCF on chromatin states, sequence ontologies, and regulatory variants. Regions with higher DeepGCF score play a more important role in regulatory activities and show heritability enrichment in human complex traits and diseases. Our DeepGCF approach shows a promising application on the comparison of cross-species functional conservation, and the model framework can be easily adapted to other species. By expanding the model to integrate the functional profiles of multiple species, including human, mouse, pig, cattle, and other livestock animals in the future, the functional conservation information will provide additional insight into the genetic and evolutionary mechanisms behind complex traits and diseases.

genetics↗

bioRxiv2022

Protease inhibitor ASP enhances freezing tolerance by inhibiting protein degradation in Kumquat

Cold acclimation is a complex biological process leading to the development of freezing tolerance in plants. In this study, we demonstrated that cold-induced expression of protease inhibitor FmASP in a citrus relative species kumquat (Fortunella margarita (Lour.) Swingle) contributes to its freezing tolerance by regulating protein degradation. First, we found that only cold-acclimated kumquat plants, although with extensive leaf cellular damage during freezing, are able to resume their normal growth upon stress relief. To dissect the impact of cold acclimation on this extraordinary freezing tolerance, we performed protein abundance assay and quantitative proteomics analysis of kumquat leaves subjected to cold acclimation (4 {degrees}C), freezing treatment (-10 {degrees}C) and post-stress recovery (25 {degrees}C). FmASP and a few non-specific proteases were identified as differentially expressed proteins induced by cold acclimation and associated with stable protein abundance throughout the course of freezing treatment. FmASP was further characterized as a robust inhibitor that inhibits the degradation capacity of multiple proteases. In addition, heterogeneous expression of FmASP in Arabidopsis confirmed its positive function in freezing tolerance. Finally, we proposed a working model of FmASP and illustrated how this extracellular-localized protease inhibitor protects proteins from degradation and consequently maintains essential cellular function for freezing stress recovery. These findings revealed the important role of protease inhibition on freezing response and provide insights on how this role may help develop new strategies to enhance plant freezing tolerance. One-sentence summaryA protease inhibitor of Fortunella margarita enhances protein stability and freezing tolerance by regulating non-specific protease degradation

plant biology↗

bioRxiv2022

An Improved Linear Mixed Model for Multivariate Genome-Wide Association Studies

Current methods of multivariate analysis require complete multivariate phenotypes from each individual and have a computational time complexity of O(n2) per SNP, where n is the sample size. We develop an efficient genomic multivariate analysis tool (GMAT) for genome-wide association studies of multiple correlated traits. The new method can handle incomplete multivariate data with missing records and reduce the time complexity to O(n) per SNP. Simulation studies based on known genotypes and phenotypes of actual populations show that GMAT has increased the statistical power with a proper control of false positivity for association studies compared to the conventional linear mixed model (LMM) that removes individuals with incomplete records. Applications to a balanced donkey data and an unbalanced yeast data show that the computational efficiency of the new method has been increased about tens of times faster than the conventional LMM analysis. The GMAT package can be downloaded at https://github.com/chaoning/GMAT.

bioinformatics↗

bioRxiv2021

α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization

The centrosome, composed of a pair of centrioles (mother and daughter centrioles) and pericentriolar material, is mainly responsible for microtubule nucleation and anchorage in animal cells. The subdistal appendage (SDA) is a centriolar structure located at the subdistal region on the mother centriole, and it functions in microtubule anchorage. However, the molecular composition and detailed structure of SDA remain largely unknown. Here, we identified a-taxilin and r-taxilin as new SDA components, which form a complex via their coiled-coil domains and serve as a new subgroup during SDA hierarchical assembly. Their SDA localization is dependent on ODF2, and -taxilin recruits CEP170 to the SDA. Functional analyses suggest that -taxilin and {gamma}-taxilin are responsible for centrosomal microtubule anchorage during interphase, as well as for proper spindle orientation during metaphase. Altogether, our results shed light on the molecular components and functional understanding of the SDA hierarchical assembly and microtubule organization.

cell biology↗

bioRxiv2020

Conversion between 100-million-year-old duplicated genes contributes to rice subspecies divergence

Extensive sequence similarity between duplicated gene pairs produced by paleo-polyploidization may result from illegitimate recombination between homologous chromosomes. The genomes of Asian cultivated rice Xian/indica (XI) and Geng/japonica (GJ) have recently been updated, providing new opportunities for investigating on-going gene conversion events. Using comparative genomics and phylogenetic analyses, we evaluated gene conversion rates between duplicated genes produced by polyploidization 100 million years ago (mya) in GJ and XI. At least 5.19%-5.77% of genes duplicated across three genomes were affected by whole-gene conversion after the divergence of GJ and XI at ~0.4 mya, with more (7.77%-9.53%) showing conversion of only gene portions. Independently converted duplicates surviving in genomes of different subspecies often used the same donor genes. On-going gene conversion frequency was higher near chromosome termini, with a single pair of homoeologous chromosomes 11 and 12 in each genome most affected. Notably, on-going gene conversion has maintained similarity between very ancient duplicates, provided opportunities for further gene conversion, and accelerated rice divergence. Chromosome rearrangement after polyploidization may result in gene loss, providing a basis for on-going gene conversion, and may have contributed directly to restricted recombination/conversion between homoeologous regions. Gene conversion affected biological functions associated with multiple genes, such as catalytic activity, implying opportunities for interaction among members of large gene families, such as NBS-LRR disease-resistance genes, resulting in gene conversion. Duplicated genes in rice subspecies generated by grass polyploidization ~100 mya remain affected by gene conversion at high frequency, with important implications for the divergence of rice subspecies. One-sentence summaryOn-going gene conversion between duplicated genes produced by 100 mya polyploidization contributes to rice subspecies divergence, often involving the same donor genes at chromosome termini.

bioinformatics↗

bioRxiv2020

Inter-relationships between changes in stress, mindfulness, and dynamic functional connectivity

We conducted a study to understand how dynamic functional brain connectivity contributes to the moderating effect of trait mindfulness on the stress response. 40 participants provided subjective reports of stress, cortisol assays, and functional MRI before and after undergoing a social stressor. Self-reported trait mindfulness was also collected. Experiencing stress led to significant decreases in the prevalence of a connectivity state previously associated with mindfulness, but no changes in two connectivity states with prior links to arousal. Connectivity did not return to baseline 30 minutes after stress. Higher trait mindfulness was associated with attenuated affective and neuroendocrine stress response, and smaller decreases in the mindfulness-related connectivity state. In contrast, we found no association between affective response and functional connectivity. Taken together, these data allow us to construct a preliminary brain-behaviour model of how mindfulness dampens stress reactivity.

neuroscience↗

bioRxiv2019

Mitochondrial dynamics quantitatively revealed by STED nanoscopy with an enhanced squaraine variant probe

Mitochondria play a critical role in generating energy to support the entire lifecycle of biological cells, yet it is still unclear how their morphological structures evolve to regulate their functionality. Conventional fluorescence microscopy can only provide [~]300 nm resolution, which is insufficient to visualize mitochondrial cristae. Here, we developed an enhanced squaraine variant dye (MitoESq-635) to study the dynamic structures of mitochondrial cristae in live cells at superresolution. The low saturation intensity and high photostability make it ideal for long-term, high-resolution STED nanoscopy. We demonstrate the time-lapsed imaging of the mitochondrial inner membrane over 50 minutes in living HeLa cells at 35.2 nm resolution for the first time. The forms of the cristae during mitochondrial fusion and fission can be clearly resolved. Our study demonstrates the emerging capability of optical STED nanoscopy to investigate intracellular physiological processes at nanoscale resolution for long periods of time with minimal phototoxicity.

biophysics↗

bioRxiv2019

Spread of pathological α-synuclein from urogenital nerves initiates multiple system atrophy-like symptoms

Multiple system atrophy (MSA) is a fatal adult-onset movement disorder with autonomic failures, especially urogenital dysfunction. The neuropathological feature of MSA is the accumulation of misfolded -synuclein (-Syn) in the nervous system. Here, we show that misfolded -Syn exist in nerve terminals in detrusor (DET) and external urethral sphincter (EUS) of patients with MSA. Moreover, -Syn preformed fibrils inoculated into the EUS or DET in TgM83+/- mice initiated the transmission of misfolded -Syn from the lower urinary tract to brain, and these mice developed -Syn inclusion pathology through micturition reflex pathways along with urinary dysfunction and motor impairments. These findings indicate that spreading of misfolded -Syn from the autonomic control of the lower urinary tract to the brain via micturition reflex pathways induces autonomic failure and motor impairments. These results provide important new insights into the pathogenesis of MSA as well as highlight potential targets for early detection and therapeutics.

neuroscience↗

bioRxiv2019

Cognitive vulnerability to sleep deprivation is robustly associated with two dynamic connectivity states

Robustly linking dynamic functional connectivity (DFC) states to behaviour is an important goal of the fledgling research using these methods. Previously, using a sliding window approach, we identified two dynamic connectivity states (DCS) linked to arousal. Here, in an independent dataset, 32 healthy participants underwent two sets of resting-state functional magnetic resonance imaging (fMRI) scans, once in a well-rested state and once after a single night of total sleep deprivation. Using a temporal differencing method, DFC and clustering analysis on the resting state fMRI data revealed five centroids that were highly correlated with those found in previous work, including the two states associated with high and low arousal. Individual differences in cognitive vulnerability to sleep deprivation were measured using changes in Psychomotor Vigilance Test (PVT) performance (lapses and median reaction speed), Changes in the percentage of time spent in the arousal states from the well-rested to the sleep-deprived condition specifically were correlated with declines in PVT performance. Our results provide good evidence of the validity and reproducibility of DFC measures, particularly with regard to measuring arousal and attention, and are an encouraging base from which to build a chronnectome mapping DCS to cognition.

neuroscience↗

bioRxiv2018

Dynamic functional connectivity markers of objective trait mindfulness

While mindfulness is commonly viewed as a skill to be cultivated through practice, untrained individuals can also vary widely in dispositional mindfulness. Prior research has identified static neural connectivity correlates of this trait. Here, we use dynamic functional connectivity (DFC) analysis of resting-state fMRI to study time-varying connectivity patterns associated with naturally varying and objectively measured trait mindfulness. Participants were selected from the top and bottom tertiles of performers on a breath-counting task to form high trait mindfulness (HTM; N = 21) and low trait mindfulness (LTM; N = 18) groups. DFC analysis of resting state fMRI data revealed that the HTM group spent significantly more time in a brain state associated with task-readiness - a state characterized by high within-network connectivity and greater anti-correlations between task-positive networks and the default-mode network (DMN). The HTM group transitioned between brain states more frequently, but the dwell time in each episode of the task-ready state was equivalent between groups. These results persisted even after controlling for vigilance. Across individuals, certain connectivity metrics were weakly correlated with self-reported mindfulness as measured by the Five Facet Mindfulness Questionnaire, though these did not survive multiple comparisons correction. In the static connectivity maps, HTM individuals had greater within-network connectivity in the DMN and the salience network, and greater anti-correlations between the DMN and task-positive networks. In sum, DFC features robustly distinguish HTM and LTM individuals, and may be useful biological markers for the measurement of dispositional mindfulness.

neuroscience↗