Biology subjects

Tan, S.

Publications and source records attributed to Tan, S..

122 records · Page 7Linked to original sources

bioRxiv2020

Transcriptional analysis of Camellia oleifera inoculated with Colletotrichum fructicola from Different Geographic regions

Anthracnose, caused by Colletotrichum. Spp., is an important disease affecting oil tea (Camellia oleifera). Extensive molecular studies have demonstrated that Colletotrichum fructicola is the dominant pathogen of oil tea anthracnose in China. The study aims to investigate differences in molecular processes and regulatory genes at different stages of infection of C. fructicola, to aide in understanding differences in pathogenic mechanisms of C. fructicola of different geographic populations. Materials and Methods: We compared the pathogenicity of C. fructicola from different populations (Wuzhishan, Hainan province and Shaoyang, Hunan province), and gene expression of representative strains of the two populations before and after inoculation in oil tea using RNA sequencing. In results we found that C. fructicola from Wuzhishan has a stronger ability to infect and impact oil tea leaf tissue. Up-regulated genes in oil tea following infection with the two geographic populations were associated with a number of ribosome-related GO terms and ribosome metabolic related KEGG pathways, and were significantly enriched in galactosidase activity, glutamine family amino acid metabolism, arginine and proline metabolism. In addition, up-regulated gene lists associated with infection in the Wuzhishan strains were significantly enriched purine metabolism pathways as well, while Shaoyang strains were not significantly enriched in these processes. Differences in gene expression were indicative of greater active transcription and translation in the Wuzhishan population while more active glycoprotein metabolism was observed following inoculation with strains from Shaoyang. These results indicate that C. fructicola obtained sugars and amino acids from oil tea tissue to resist host immune pressure. Moreover, more active in transcriptional and translational activity and the greater regulation of purine metabolism pathway in the Wuzhishan strain might contribute to its stronger pathogenicity.

microbiology↗

bioRxiv2020

Neural stem cells traffic functional mitochondria via extracellular vesicles to correct mitochondrial dysfunction in target cells

Neural stem cell (NSC) transplantation induces recovery in animal models of central nervous system (CNS) diseases. Although the replacement of lost endogenous cells was originally proposed as the primary healing mechanism of NSC grafts, it is now clear that transplanted NSCs operate via multiple mechanisms, including the horizontal exchange of therapeutic cargoes to host cells via extracellular vesicles (EVs). EVs are membrane particles trafficking nucleic acids, proteins, metabolites and metabolic enzymes, lipids and entire organelles. However, the function and the contribution of these cargoes to the broad therapeutic effects of NSCs is yet to be fully understood. Mitochondrial dysfunction is an established feature of several inflammatory and degenerative CNS disorders, most of which are potentially treatable with exogenous stem cell therapeutics. Herein we investigated the hypothesis that NSCs release and traffic functional mitochondria via EVs to restore mitochondrial function in target cells. Untargeted proteomics revealed a significant enrichment of mitochondrial proteins spontaneously released by NSCs in EVs. Morphological and functional analyses confirmed the presence of ultrastructurally intact mitochondria within EVs (Mito-EVs) with conserved membrane potential and respiration. We found that the transfer of Mito-EVs to mtDNA-deficient L929 Rho0 cells rescued mitochondrial function and increased Rho0 cell survival. Furthermore, the incorporation of Mito-EVs into inflammatory professional phagocytes restored normal mitochondrial dynamics and cellular metabolism and reduced the expression of pro-inflammatory markers in target cells. When transplanted in an animal model of multiple sclerosis, exogenous NSCs actively transferred mitochondria to mononuclear phagocytes and induced a significant amelioration of clinical deficits. Our data provide the first evidence that NSCs deliver functional mitochondria to target cells via Mito-EVs, paving the way for the development of novel (a)cellular approaches aimed at restoring mitochondrial dysfunction not only in multiple sclerosis, but also in degenerative neurological diseases.

neuroscience↗

bioRxiv2019

Hierarchical assembly of the MLL1 core complex within a biomolecular condensate regulates H3K4 methylation

The enzymes that regulate histone H3 lysine 4 (H3K4) methylation are required for cellular differentiation and development and are often mutated in human disease. Mixed Lineage Leukemia protein-1 (MLL1) is a member of the SET1 family of histone H3 lysine 4 methyltransferases, which require interaction with a conserved sub-complex consisting of WDR5, RbBP5, Ash2L and DPY30 (WRAD2) for maximal activity. It is currently unclear how assembly of SET1 family complexes is involved in the spatiotemporal control of H3K4 methylation in eukaryotic genomes. In this investigation, we systematically characterized the hydrodynamic and kinetic properties of a reconstituted human MLL1 core complex and found that its assembly is highly concentration and temperature dependent. Consistent with a hierarchical assembly pathway, we found that the holo-complex assembles through interactions between the MW and RAD2 sub-complexes, which is correlated with enzymatic activity. Surprisingly, we found that the disassembled state is favored at physiological temperatures, and that this thermodynamic barrier can be overcome under conditions that induce high-local concentrations of subunits in phase separated compartments. Combining this data with the observation that MLL1 primary sequence contains large regions of intrinsic disorder, we propose a "swinging-domain" model in which the interaction between a tethered MW subcomplex and multiple nucleosome-RAD2 complexes is regulated by the rapid formation or dissolution of biomolecular condensates, such as occurs in transcription factories. This model provides an elegant "switch-like" mechanism for spatiotemporal control of H3K4 methylation within eukaryotic genomes.

biochemistry↗

bioRxiv2019

Expressing remorin in animal cells forms filamentous structure unraveling the mechanism of plasmodesmata biogenesis

Plasmodesmata (PD) are crucial structures for intercellular communication in multicellular plants with remorins being their crucial plant-specific structural and functional constituents. The PD biogenesis is an intriguing but poorly understood process. By expressing an Arabidopsis remorin protein in mammalian cells, we have reconstituted a PD-like filamentous structure, termed remorin filament (RF), connecting neighboring cells physically and physiologically. Notably, RFs are capable of transporting macromolecules intercellularly, in a way similar to plant PD. With further super-resolution microscopic analysis and biochemical characterization, we found that RFs are also composed of actin filaments, forming the core skeleton structure, aligned with the remorin protein. This unique heterologous filamentous structure might explain the molecular mechanism for remorin function as well as PD construction. Furthermore, remorin protein exhibits a specific distribution manner in the plasma membrane in mammalian cells, representing a lipid nanodomain, depending on its lipid modification status. Our studies not only provide crucial insights into the mechanism of PD biogenesis, but also uncovers unsuspected fundamental mechanistic and evolutionary links between intercellular communication systems of plants and animals. SignificanceRemorin is rising as a crucial lipid microdomain marker, as well as an essential component of plasmodesmata in plants. However, the biological role of remorin in plants is elusive. With a heterologous system, we found that remorin expression is able to form intercellular filamentous structure, namely remorin filament (RF), connecting neighboring mammalian cells functionally. By employing multiple approaches, we tested the functionality of RFs, as well as investigated their structures. RFs highly resemble plant plasmodesmata, in many ways, such as its morphology, molecular constitutes, and its ability to transport macromolecules intercellularly. Our study provides novel insights into the biogenesis of plasmodesmata and uncovers fundamental evolutionary links in molecular construction of intercellular connections in both plants and animals.

cell biology↗

bioRxiv2019

ASlive: a database for alternative splicing atlas in livestock animals

We present in this study the development and implementation of a database for alternative splicing atlas in livestock animals (ASlive.org). Alternative splicing is an important biological process whose precision must be tightly regulated during growth and development. Using publicly available RNASeq data sets across many tissues, cell types, and biological conditions totaling 28.6 tera bases, we built a database of alternative splicing events in five major livestock animal species (cattle, sheep, pigs, horses, and chickens). The database contains many types of information on alternative splicing events, including basic information such as genomic locations, genes, and event types, quantitative measurements of alternative splicing in the form of percent spliced in (PSI), overlap with known DNA variants, as well as orthologous events across different lineage groups. This database, the first of its kind in livestock animals, will provide a useful exploratory tool to assist functional annotation of animal genomes.

genomics↗

bioRxiv2019

A lipid code-dependent phosphoswitch directs PIN-mediated auxin efflux in Arabidopsis development

Directional intercellular transport of the phytohormone auxin mediated by PIN FORMED (PIN) efflux carriers plays essential roles in both coordinating patterning processes and integrating multiple external cues by rapidly redirecting auxin fluxes. Multilevel regulations of PIN activity under internal and external cues are complicated; however, the underlying molecular mechanism remains elusive. Here we demonstrate that 3-Phosphoinositide-Dependent Protein Kinase1 (PDK1), which is conserved in plants and mammals, functions as a molecular hub integrating the upstream lipid signalling and the downstream substrate activity through phosphorylation. Genetic analysis uncovers that loss-of-function Arabidopsis mutant pdk1.1 pdk1.2 exhibits a plethora of abnormalities in organogenesis and growth, due to the defective PIN-dependent auxin transport. Further cellular and biochemical analyses reveal that PDK1 phosphorylates D6 Protein Kinase to facilitate its activity towards PIN proteins. Our studies establish a lipid-dependent phosphorylation cascade connecting membrane composition-based cellular signalling with plant growth and patterning by regulating morphogenetic auxin fluxes.

plant biology↗

bioRxiv2019

Effects of Five Products on Gut Microbiota and Short-Chain Fatty Acids of Obese Rats

The effects of banana powder(BP), konjac powder(KP), resistant dextrin(RD), corn starch(CS) and L-carnitine(LC) on gut microbiota and metabolites (SCFA) were evaluated in order to provide basic data for the development of weight-loss functional food. The gut microbiota profile using 16S V4 rDNA high-throughput sequencing technique suggested that the rats of RD, BP and CS group developed an increased richness and diversity in the gut bacterial community, while the abundance of the KP and LC group was not enhanced obviously. Verrucomicrobiaceae, Coprococcus-2 and Lachnospiraceae were the main bacterial genera in the CS, BP and RD group respectively, indicating their potential use as prebiotics. On the other hand, rats fed with BP, KP, CS and RD contributed higher total SCFA than those feeding with LC diet. Thus, RD, BP, CS, KP could moduate gut microbiota and increase the SCFA concentration, while the effect of LC are not apparent.

microbiology↗

bioRxiv2019

Dorsoventral dissociation of Hox gene expression underpins the diversification of molluscs

Unlike the Hox genes in arthropods and vertebrates, those in molluscs show diverse expression patterns and, with some exceptions, have generally been described as lacking the canonical staggered pattern along the anterior-posterior (AP) axis. This difference is unexpected given that almost all molluscs share highly conserved early development. Here, we show that molluscan Hox expression can undergo dynamic changes, which may explain why previous research observed different expression patterns. Moreover, we reveal that a key character of molluscan Hox expression is that the dorsal and ventral expression is dissociated. We then deduce a generalized molluscan Hox expression model, including conserved staggered Hox expression in the neuroectoderm on the ventral side and lineage-specific dorsal expression that strongly correlates with shell formation. This generalized model clarifies a long-standing debate over whether molluscs possess staggered Hox expression and it can be used to explain the diversification of molluscs. In this scenario, the dorsoventral dissociation of Hox expression allows lineage-specific dorsal and ventral patterning in different clades, which may have permitted the evolution of diverse body plans in different molluscan clades.

developmental biology↗

bioRxiv2018

Access COI barcode efficiently using high throughput Single End 400 bp sequencing

O_LIOver the last decade, the rapid development of high-throughput sequencing platforms has accelerated species description and assisted morphological classification through DNA barcoding. However, constraints in barcoding costs led to unbalanced efforts which prevented accurate taxonomic identification for biodiversity studies.\nC_LIO_LIWe present a high throughput sequencing approach based on the HIFI-SE pipeline which takes advantage of Single-End 400 bp (SE400) sequencing data generated by BGISEQ-500 to produce full-length Cytochrome c oxidase subunit I (COI) barcodes from pooled polymerase chain reaction amplicons. HIFI-SE was written in Python and included four function modules of filter, assign, assembly and taxonomy.\nC_LIO_LIWe applied the HIFI-SE to a test plate which contained 96 samples (30 corals, 64 insects and 2 blank controls) and delivered a total of 86 fully assembled HIFI COI barcodes. By comparing to their corresponding Sanger sequences (72 sequences available), it showed that most of the samples (98.61%, 71/72) were correctly and accurately assembled, including 46 samples that had a similarity of 100% and 25 of ca. 99%.\nC_LIO_LIOur approach can produce standard full-length barcodes cost efficiently, allowing DNA barcoding for global biomes which will advance DNA-based species identification for various ecosystems and improve quarantine biosecurity efforts.\nC_LI

ecology↗

bioRxiv2018

Loss Of Kat2a Enhances Transcriptional Noise And Depletes Acute Myeloid Leukemia Stem-Like Cells

Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective myelo-monocytic differentiation. Its pathogenesis comprises subversion of transcriptional regulation, through mutation and by hijacking normal chromatin regulation. Kat2a is a histone acetyltransferase central to promoter activity that we recently associated with stability of pluripotency networks, and identified as a genetic vulnerability in AML. Through combined chromatin profiling and single-cell transcriptomics, we demonstrate that Kat2a contributes to leukemia propagation through homogeneity of transcriptional programs and preservation of leukemia stem-like cells. Kat2a loss reduces transcriptional bursting frequency in a subset of gene promoters, generating enhanced variability of transcript levels but minimal effects on mean gene expression. Destabilization of target programs shifts cellular equilibrium out of self-renewal towards differentiation. We propose that control of transcriptional variability is central to leukemia stem-like cell propagation, and establish a paradigm exploitable in different tumors and at distinct stages of cancer evolution.

cancer biology↗

bioRxiv2018

Unbiased Age-Appropriate Structural Brain Atlases for Chinese Pediatrics

In magnetic resonance imaging (MRI) studies of children brain development, structural brain atlases usually serve as important references of pediatric population in which individual images are spatially normalized into a common or standard stereotactic space. However, the existing popular children brain atlases (e.g., National Institutes of Health pediatric atlases, NIH-PD atlases) are made mostly based on MR images from Western populations, and are thus insufficient to characterize the brains of Chinese children due to the neuroanatomical differences that are relevant to genetic and environmental factors. By collecting high-quality T1- and T2- weighted MR images from 328 typically developing Chinese children aged from 6 to 12 years old, we created a set of age-appropriate Chinese pediatric (CHN-PD) atlases using an unbiased template construction algorithm. The CHN-PD atlases included the head/brain templates, the symmetric brain template, the gender-specific brain templates and the corresponding tissue probability atlases. Moreover, the atlases contained multiple age-specific templates with a one-year interval. A direct comparison of the CHN-PD and the NIH-PD atlases revealed remarkable anatomical differences bilaterally in the lateral frontal and parietal regions and somatosensory cortex. While applying the CHN-PD atlases to two independent Chinese pediatric datasets (N = 114 and N = 71, respectively), machine-learning regression approaches revealed higher prediction accuracy on brain ages than the usage of NIH-PD atlases. These results suggest that the CHN-PD brain atlases are necessary and important for future typical and atypical developmental studies in Chinese pediatric population. Currently, the CHN-PD atlases have been released on the NITRC website (https://www.nitrc.org/projects/chn-pd).

neuroscience↗

bioRxiv2018

YB-1 Is Critical For The Genesis And Progression Of KRAS Mutated Human Breast Cancer

Breast cancer heterogeneity has made it challenging to elucidate shared mechanisms that underpin properties that are critical to their growth in vivo. Here, we interrogate the role of YB-1 protein in the in vivo tumorigenic activity of de novo well as cell line models of human breast cancer. Short-hairpin RNA-mediated knockdown of YB-1 in MDA-MB-231 cells blocked both their local tumour-forming and lung-colonizing activity in transplanted immunodeficient mice. YB-1 knockdown also revealed its important role at early stages of human mammary cell transformation in the generation of invasive ductal carcinoma and ductal carcinoma in situ produced in mice transplanted with freshly isolated human mammary cells transduced, respectively, with KRASG12D, or myristoylated-AKT1. Conversely, upregulated expression of YB-1 in the poorly tumorigenic T47D cells enhanced this activity. Mechanistically, reducing YB-1 levels in MDA-MB-231 cells impaired their induction of HIF1, and G3BP1, known YB-1 translational targets and key elements of a stress-adaptive program.

cancer biology↗

bioRxiv2018

ADS-J1 Disaggregates Semen-derived Amyloid Fibrils

Semen-derived amyloid fibrils, composing SEVI (semen-derived enhancer of viral infection) fibrils and SEM1 fibrils, could remarkably enhance HIV-1 sexual transmission and thus, are potential targets for the development of an effective microbicide. Previously, we found that ADS-J1, apart from being an HIV-1 entry inhibitor, could also potently inhibit seminal amyloid fibrillization and block fibril-mediated enhancement of viral infection. However, the remodeling effects of ADS-J1 on mature seminal fibrils were unexplored. Herein, we investigated the capacity of ADS-J1 to disassemble seminal fibrils and the potential mode of action by applying several biophysical and biochemical measurements, combined with molecular dynamic (MD) simulations. We found that ADS-J1 effectively remodeled SEVI, SEM186-107 fibrils and endogenous seminal fibrils. Unlike epi-gallocatechin gallate (EGCG), a universal amyloid fibril breaker, ADS-J1 disaggregated SEVI fibrils into monomeric peptides, which was independent of oxidation reaction. MD simulations revealed that ADS-J1 displayed strong binding potency to the full-length PAP248-286 via electrostatic interactions, hydrophobic interactions and hydrogen bonds. ADS-J1 might initially bind to the fibrillar surface and then occupy the amyloid core, which eventually lead to fibril disassembly. Furthermore, the binding of ADS-J1 with PAP248-286 might induce conformational changes of PAP248-286. Disassembled PAP248-286 might not be favor to re-aggregate into fibrils. ADS-J1 also exerts abilities to remodel a panel of amyloid fibrils, including A{beta}1-42, hIAPP1-37 and EP2 fibrils. ADS-J1 displays promising potential to be a combination microbicide and an effective lead-product to treat amyloidogenic diseases.

pharmacology and toxicology↗

bioRxiv2017

Paternally inherited noncoding structural variants contribute to autism

The genetic architecture of autism spectrum disorder (ASD) is known to consist of contributions from gene-disrupting de novo mutations and common variants of modest effect. We hypothesize that the unexplained heritability of ASD also includes rare inherited variants with intermediate effects. We investigated the genome-wide distribution and functional impact of structural variants (SVs) through whole genome analysis ([≥]30X coverage) of 3,169 subjects from 829 families affected by ASD. Genes that are intolerant to inactivating variants in the exome aggregation consortium (ExAC) were depleted for SVs in parents, specifically within fetal-brain promoters, UTRs and exons. Rare paternally-inherited SVs that disrupt promoters or UTRs were over-transmitted to probands (P = 0.0013) and not to their typically-developing siblings. Recurrent functional noncoding deletions implicate the gene LEO1 in ASD. Protein-coding SVs were also associated with ASD (P = 0.0025). Our results establish that rare inherited SVs predispose children to ASD, with differing contributions from each parent.

genomics↗