Biology subjects

Xiong, L.

Publications and source records attributed to Xiong, L..

47 records · Page 3Linked to original sources

bioRxiv2020

CD127 imprints functional heterogeneity to diversify monocyte responses in human inflammatory diseases

Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.

immunology↗

bioRxiv2020

Jejunal barrier dysfunction of Datong Yak with high proportion concentrate dietary during the cold season

The current study aimed to investigate the damage of long-term high concentrate diet feeding pattern on Yak jejunal structure, physiological function and protein composition during cold season. Twelve Datong male Yak (Bos grunniens) with the same age from cold season were randomly selected and slaughtered to determine Yak jejunal digestive enzyme activity, morphology and protein composition on different feeding patterns in Tibetan Plateau. The results showed that Yak jejunum digestive enzyme activity and morphology of grazing reared group were better than those in the intensively reared group. A total of 96 differentially expressed proteins were identified by label-free Mass Spectrometry (MS), which could be concluded to two predominant themes: protein structure and inflammatory response. Nine differentially expressed proteins were correlated in Yak jejunum damage in different feeding patterns. According to our study, feeding patterns resulted in the differences in Yak jejunum physiological function, morphology and protein composition. Our results confirmed that feeding of long-term high concentrate diet could damage the jejunum epithelial morphology and function.

genetics↗

bioRxiv2020

Macroscale network feedback structure of transcriptome during cell fate transition

Embryonic development is characterized by series of cell fate transitions, during which non-linear feedback of signaling events and network dynamics in the transcriptome are instrumental to determine differentiation outcomes. Changes in selected genes or pathways have been described extensively, but a system-level understanding of gene regulatory network regulation is still lacking. Leveraging time-series data from single-cell transcriptome profiling of developing mouse embryos, we collapsed dynamic gene expressions into changes in 14 core biological processes, and constructed an ordinary differential equation-based machine learning model of the transcriptomic network to capture its feedback structure. We evaluated the polarity and magnitude of direct pairwise causal relationships between biological processes and identified higher-order feedback loops that dominate system behavior. Despite heterogeneous expressions at the gene level, we find that the transcriptome at the macroscale level has a feedback structure that is intrinsically stable and robust. We show the pivotal role of intracellular signaling in driving systemic changes and uncover the importance of homeostatic process and establishment of localization in regulating network dynamics. Local regulatory structures represent domain-specific regulations that are essential to cell fate transition, especially lipid metabolic process. Together, this study provides a holistic picture of transcriptomic network dynamics during mouse organogenesis, offering insight into key aspects of information flow in the transcriptome that control cell fate transition. Conflict of interest statementThe authors declare no potential conflicts of interest. FundingThe authors received no funding for this study. Author contributionsConceptualization: LX; Methodology: LX, WAS, and JDS; Data Curation: LX; Investigation: LX and WAS; Formal Analysis: LX and WAS; Visualization: WAS and LX; Writing - review & editing: LX and WAS.

systems biology↗

bioRxiv2020

MosaicBase: A Knowledgebase of Postzygotic Mosaic Variants in Noncancer Diseases and Asymptomatic Human Individuals

Mosaic variants resulting from postzygotic mutations are prevalent in the human genome and play important roles in human diseases. However, except for cancer-related variant collections, there are no collections of mosaic variants in noncancer diseases and asymptomatic individuals. Here, we present MosaicBase (http://mosaicbase.cbi.pku.edu.cn/ or http://49.4.21.8:8000/), a comprehensive database that includes 6,698 mosaic variants related to 269 noncancer diseases and 27,991 mosaic variants identified in 422 asymptomatic individuals. The genomic and phenotypic information for each variant was manually extracted and curated from 383 publications. MosaicBase supports the query of variants with Online Mendelian Inheritance in Man (OMIM) entries, genomic coordinates, gene symbols, or Entrez IDs. We also provide an integrated genome browser for users to easily access mosaic variants and their related annotations within any genomic region. By analyzing the variants collected in MosaicBase, we found that mosaic variants that directly contribute to disease phenotype showed features distinct from those of variants in individuals with a mild or no phenotype in terms of their genomic distribution, mutation signatures, and fraction of mutant cells. MosaicBase will not only assist clinicians in genetic counseling and diagnosis but also provide a useful resource to understand the genomic baseline of postzygotic mutations in the general human population.

bioinformatics↗

bioRxiv2019

Germline and somatic genetic variants in the p53 pathway interact to affect cancer risk, progression and drug response

Insights into oncogenesis derived from cancer susceptibility loci could facilitate better cancer management and treatment through precision oncology. However, therapeutic applications have thus far been limited by our current lack of understanding regarding both their interactions with somatic cancer driver mutations and their influence on tumorigenesis. Here, by integrating germline datasets relating to cancer susceptibility with tumour data capturing somatically-acquired genetic variation, we provide evidence that single nucleotide polymorphism (SNPs) and somatic mutations in the p53 tumor suppressor pathway can interact to influence cancer development, progression and treatment response. We go on to provide human genetic evidence of a tumor-promoting role for the pro-survival activities of p53, which supports the development of more effective therapy combinations through their inhibition in cancers retaining wild-type p53. SignificanceWe describe significant interactions between heritable and somatic genetic variants in the p53 pathway that affect cancer susceptibility, progression and treatment response. Our results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and identify novel therapeutic targets.

cancer biology↗

bioRxiv2019

Heritable genetic variants in key cancer genes link cancer risk with anthropometric traits

Inherited genetic variants in tumour suppressors and oncogenes can increase the cancer risk, but little is known about their influence on anthropometric traits. Through the integration of inherited and somatic cancer genetic data, we define functional single nucleotide polymorphisms (SNPs) associated with cancer risk and explore potential pleiotropic associations with anthropometic traits in a cohort of 500,000 individuals. We identify three regulatory SNPs for three important cancer genes that associate with both anthropometric traits and cancer risk. We describe a novel association of a SNP in TP53 (rs78378222) with height, lean body mass measures and basal metabolic rate, as well as validating its known associations with brain and non-melanomatous skin cancer susceptibility. Our results clearly demonstrate that heritable variants in key cancer genes can associate with both differential cancer risk and anthropometric traits in the general population, thereby lending support for a role of genetics in linking these human phenotypes.

genetics↗

bioRxiv2019

Electroacupuncture at Governor Vessel improves neurobehavioral function via reduction of complexin1

Electroacupuncture at Governor Vessel (GV), as a traditional chinese medicine, has been proved that it can reduce scar and promote axon regeneration. However, the underlying mechanism remains unclear. Herein, complexin1 (CPLX1), as a candidate protein, was found using protein chip. Therefore, using a CRISPR/Cas9 knockout approach, we deleted CPLX1 specifically in the SD rats to assess the role of CPLX1 in GV treatment. Additionally, eIF5A1 stimulate the translation of CPLX1 with PPG sequence, we attempt to uncover whether eIF5A1 play a role in the GV treatment. In fact, GV can reduce scar and promote axon regeneration after SCC. CPLX1-/+ SCC rats demonstrated that decreased CPLX1 improved the microenvironment of injured area via reducing the components of fibrotic scar and further enhanced the synaptic plasticity, which benefit the regeneration of axons. And eIF5A1 could regulate the expression of CPLX1 in the process of GV treatment. Therefore, GV contributes to axon regeneration and synapse plasticity via eIF5A1 regulating CPLX1 following SCC, providing a convincible mechanism for improving the therapeutic efficacy of GV for SCC.

neuroscience↗

bioRxiv2019

Arabidopsis Proteome and the Mass Spectral Assay Library

Arabidopsis is an important model organism and the first plant with its genome sequenced. Knowledge from studying this species has either direct or indirect applications to agriculture and human health. Quantitative proteomics by data-independent acquisition (SWATH/DIA-MS) was recently developed and considered as a high-throughput targetedlike approach for accurate proteome quantitation. In this approach, a high-quality and comprehensive library is a prerequisite. Here, we generated a protein expression atlas of 10 organs of Arabidopsis and created a library consisting of 15,514 protein groups, 187,265 unique peptide sequences, and 278,278 precursors. The identified protein groups correspond to ~56.5% of the predicted proteome. Further proteogenomics analysis identified 28 novel proteins. We subsequently applied DIA-mass spectrometry using this library to quantify the effect of abscisic acid on Arabidopsis. We were able to recover 8,793 protein groups with 1,787 of them being differentially expressed which includes 65 proteins known to respond to abscisic acid stress. Mass spectrometry data are available via ProteomeXchange with identifier PXD012710 for data-dependent acquisition and PXD014032 for DIA analyses.\n\nO_TBL View this table:\norg.highwire.dtl.DTLVardef@1a3f799org.highwire.dtl.DTLVardef@1d4711dorg.highwire.dtl.DTLVardef@4e3f73org.highwire.dtl.DTLVardef@127a9a4org.highwire.dtl.DTLVardef@f254bb_HPS_FORMAT_FIGEXP M_TBL C_TBL

plant biology↗

bioRxiv2019

Flower-like patterns in multi-species biofilms

Diverse interactions among species within bacterial biofilms often lead to intricate spatiotemporal dynamics. The spatial structure of biofilms can determine growth and survival of different species, but the mechanisms driving formation of this structure are not fully understood. Here, we describe the emergence of complex structures in a biofilm grown from mixtures of motile and non-motile bacterial species on a soft agar surface. Time-lapse imaging shows that non-motile bacteria "hitchhike" on the motile bacteria as the latter migrate outward. The non-motile bacteria accumulate at the boundary of the colony and trigger an instability that leaves behind striking flower-like patterns. The mechanism of the front instability governing this pattern formation is elucidated by a mathematical model for the frictional motion of the colony interface, with friction depending on the local concentration of the nonmotile species along the interface. A more elaborate two-dimensional phase-field model that explicitly accounts for the interplay between growth, mechanical stress from the motile species, and friction provided by the non-motile species, fully reproduces the observed flower-like patterns.

microbiology↗

bioRxiv2018

Carbon starvation-induced lipoprotein Slp directs the synthesis of catalase and expression of OxyR regulator to protect against hydrogen peroxide stress in Escherichia coli

Escherichia coli can induce a group of stress-response proteins, including carbon starvation-induced lipoprotein (Slp), which is an outer membrane lipoprotein expressed in response to stressful environments. In this paper, slp null mutant\n\nE. coli were constructed by insertion of the group II intron, and then the growth sensitivity of the slp mutant strain was measured under 0.6% (vol/vol) hydrogen peroxide. The changes in resistance to hydrogen peroxide stress were investigated by detecting antioxidant activity and gene expression in the slp mutant strain. The results showed that deletion of the slp gene increased the sensitivity of E. coli under 0.6% (vol/vol) hydrogen peroxide oxidative stress. Analysis of the unique mapping rates from the transcriptome libraries revealed that four of thirteen remarkably up/down-regulated genes in E. coli were involved in antioxidant enzymes after mutation of the slp gene. Mutation of the slp gene caused a significant increase in catalase activity, which contributed to an increase in glutathione peroxidase activity. The katG gene was activated by the OxyR regulator, which was activated directly by 0.6% (vol/vol) hydrogen peroxide, and HPI encoded by katG was induced against oxidative stress. Therefore, the carbon starvation-induced lipoprotein Slp regulates the expression of antioxidant enzymes and the transcriptional activator OxyR in response to the hydrogen peroxide environment, ensuring that cells are protected from hydrogen peroxide oxidative stress at the level of enzyme activity and gene expression.

molecular biology↗

bioRxiv2018

Combining high-throughput micro-CT-RGB phenotyping and genome-wide association study to dissect the genetic architecture of tiller growth in rice

Traditional phenotyping of rice tillers is time consuming and labor intensive and lags behind the rapid development of rice functional genomics. Thus, dynamic phenotyping of rice tiller traits at a high spatial resolution and high-throughput for large-scale rice accessions is urgently needed. In this study, we developed a high-throughput micro-CT-RGB (HCR) imaging system to non-destructively extract 730 traits from 234 rice accessions at 9 time points. We used these traits to predict the grain yield in the early growth stage, and 30% of the grain yield variance was explained by 2 tiller traits in the early growth stage. A total of 402 significantly associated loci were identified by GWAS, and dynamic and static genetic components were found across the nine time points. A major locus associated with tiller angle was detected at nine time points, which contained a major gene TAC1. Significant variants associated with tiller angle were enriched in the 3'-UTR of TAC1. Three haplotypes for the gene were found and tiller angles of rice accessions containing haplotype H3 were much smaller. Further, we found two loci contained associations with both vigor-related HCR traits and yield. The superior alleles would be beneficial for breeding of high yield and dense planting.\n\nHighlightCombining high-throughput micro-CT-RGB phenotyping facility and genome-wide association study to dissect the genetic architecture of rice tiller development by using the indica subpopulation.

genetics↗