Biology subjects

Liao, L.

Publications and source records attributed to Liao, L..

26 records · Page 2Linked to original sources

bioRxiv2022

The Chromosome-based Genome of Paspalum vaginatum Provides New Insights into Salt-stress Adaptation

Salinization is increasingly a major factor limiting production worldwide. Revealing the mechanism of salt tolerance could help to create salt-tolerant crops and improve their yields. We reported a chromosome-scale genome sequence of the halophyte turfgrass Paspalum vaginatum, and provided structural evidence that it shared a common ancestor with Z. mays and S. bicolor. A total of 107 P. vaginatum germplasms were divided into two groups (China and foreign group) based on the re-sequenced data, and the grouping findings were consistent with the geographical origin. Genome-wide association study (GWAS) of visually scored wilting degree and withering rates identified highly significant QTL on chromosome 6. Combination with RNA-seq, we identified a significantly up-regulated gene under salt stress, which encodes High-affinity K+ Transporter 7 (PvHKT7), as strong candidates underlying the QTL. Overexpression of this gene in Arabidopsis thaliana significantly enhanced salt tolerance by increasing K+ absorption. This study adds new insights into salt-stress adaptation of P. vaginatum and serve as a resource for salt-tolerant improvement of grain crops.

genomics↗

bioRxiv2021

Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development

Development of multicellular organisms is orchestrated by persistent cell-cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals that dictate lineage specification and cell fate decisions. Current single cell RNAseq (scRNAseq) technology cannot adequately analyze cell-cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell-cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified novel gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells overexpress Lhx5 and Nkx2-1 genes, when exclusively interacting with the definitive endoderm (DE) cell. Moreover, there was a reciprocal impact on the transcriptome of the DE cells, as they tend to overexpress Rax and Gsc genes when in contact with the NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-tSNE to display the pseudo-spatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis with potential broader implication in other physiologically relevant processes. SignificancePhysical contact between neighboring cells is known to induce transcriptional changes in the interacting partners. Accurate measurement of these cell-cell contact based influences on the transcriptome is a very difficult experimental task. However, determining such transcriptional changes will highly enhance our understanding for the developmental processes. Current scRNAseq technology isolates the tissue into individual cells, making it hard to determine the potential transcriptomic changes due to its interacting partners. Here, we combined PIC-seq and computational algorithms to identify cell-type contact dependent transcriptional profiles focusing on endoderm development. We have computationally identified and experimentally validated specific gene expression patterns depending upon the presence of specific neighboring cell types. Our study suggests a new way to study cell-cell interactions for embryogenesis.

developmental biology↗

bioRxiv2021

High-throughput tandem-microwell assay for ammonia repositions FDA-Approved drugs to Helicobacter pylori infection

To date, little attempt has been made to develop new treatments for Helicobacter pylori (H. pylori), although the community is aware of the shortage of treatments for H. pylori. In this study, we developed a 192-tandem-microwell-based high-throughput-assay for ammonia that is a known virulence factor of H. pylori and a product of urease. We could identify few drugs, i.e. panobinostat, dacinostat, ebselen, captan and disulfiram, to potently inhibit the activity of ureases from bacterial or plant species. These inhibitors suppress the activity of urease via substrate-competitive or covalent-allosteric mechanism, but all except captan prevent the antibiotic-resistant H. pylori strain from infecting human gastric cells, with a more pronounced effect than acetohydroxamic acid, a well-known urease inhibitor and clinically used drug for the treatment of bacterial infection. This study offers several bases for the development of new treatments for urease-containing pathogens and to study the mechanism responsible for the regulation of urease activity.

biochemistry↗

bioRxiv2020

Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis

Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease that causes worldwide morbidity and mortality, yet there is still a lack of pharmacological therapies. Liver inflammation is an important contributor for disease progression from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). We identified HDAC inhibitor givinostat as a potent inhibitor of macrophages inflammatory activation, and aimed to evaluate the therapeutic potential of givinostat for treatment of NASH. Daily administration of givoinostat (10mg/kg) alleviated inflammation and attenuated hepatic fibrosis in methionine- and choline-deficient diet (MCD)-induced NASH mice. RNA-seq analysis of liver tissues form MCD-fed mice revealed givinostat potently blocked expression of inflammation-related genes and regulated a broad set of lipid metabolism-related genes. In hepatocyte givinostat reduced palmitic acid induced intracellular lipid accumulation. The benefit of givinostat was further confirmed in fructose, palmitate, cholesterol diet (FPC) induced NASH mice. Givinostat attenuated hepatic steatosis, inflammation as well as liver injury in FPC-induced NASH. In conclusion, givinostat appears to be efficacious in reversing diet-induced NASH, and may serve as a therapeutic agent for treatment of human NASH.View Full Text

animal behavior and cognition↗

bioRxiv2020

One New Species of the Genus Dryomys (Rodentia, Glirgae) from Xinjiang China, Dryomys Yarkandensis sp. nov

During an expedition in June 2012 in Shache county of Tarim Basin in southern Xinjiang, China, a new species of the genus Dryomys (Gliridae) has been discovered and named Dryomys yarkandensis sp. nov. It has been found obviously different from D. nitedulai in northern Xinjiang, D. laniger, D. niethammeri and D. nitedulai in Europe, which are also belong to genus Dryomys. The new species Dryomys yarkandensis sp. nov is described below. HolotypeNo. N07, an adult female collected by Chen Zhenhai in June 2012, is deposited Center for disease prevention and control of Xinjiang (Xinjiang CDC). It was obtained from oasis orchard of desert in Tarim Basin (38{degrees}29N, 77{degrees}32E), 1211-1215 m. Genus characterThere is a dark chestnut round eye. The terminal of tail is club shape, covered with dense hairs, and cannot see the scale ring in external texture. Description of the speciesThe eyes is large. The beard is long and the longest could reach 30 mm. The tail is thicker and slightly longer than body length about 10%. The terminal of the tail is fluffy. All the surface is covered with dense hairs. External figureThe color of the new species on the back is lighter than that of D. laniger, D. niethammeri and D. nitedulai in Dryomys. The length of the tail is about 110% of the body length. The length of the ears is 12.8 mm, which is 15% shorter than the other three species of Dryomys. Skull and toothThe ratio between the length of audirory bullae and the breadth of auditory bullae is 1.66 (8.35/5.02), which is larger than the other three species of D. nitedula. The habitats of the new species is harsh, drought and hot in summer but dry and cold in winter. The habitats of D. nitedula in mountain valley in northern Xinjiang is temperate, humidity and low temperature, and there are berries or orchard.

zoology↗

bioRxiv2019

Global gene expression profile during low temperature in the brain of grass carp (Ctenopharyngodon idellus)

Grass carp is an important commercial fish widely cultured in China. Large range of temperature, in particular extremely low temperature, has dramatic effects on the aquaculture of this teleost. However, there is relatively little research on the molecular responses in the fish exposed to cold. Given the limited vision of approaches targeting individual genes, we investigated the transcriptome profiles of brain in response to cold in order to comprehensively characterize molecular mechanisms behind it. This study indicated that the estrogen signaling pathway was inhibited in brain when grass carp acclimated to low temperature, while terpenoid backbone biosynthesis pathway and steroid biosynthesis pathway were significantly activated. Such a result implied the crucial role of cholesterol in cold acclimation. Moreover, plenty of differentially expressed genes associated with spliceosomes were enriched during cooling process, which suggested alternative splicing may be involved in the regulation of biological process in acclimation to temperature changes. In researches on extremely low-temperature tolerance, we identified four genes (DUSP1, HSPA6, NR4A1 and GADD45B) associated with MAPK signaling pathway. The four genes, extensively up-regulated at 4{degrees}C and remained relatively low expression at moderate temperature, were closely related with extremely cold condition. Further examination of the candidate genes can provide insights into the mechanisms of grass carp to endure extremely low temperature in the winter.

zoology↗

bioRxiv2018

WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death

Mutations in the autophagy gene WDR45 cause {beta}-propeller protein-associated neurodegeneration (BPAN); however the molecular and cellular mechanism of the disease process is largely unknown. Here we generated constitutive Wdr45 knockout (KO) mice that displayed cognitive impairments, abnormal synaptic transmission and lesions in hippocampus and basal ganglia. Immunohistochemistry analysis shows loss of neurons in prefrontal cortex and basal ganglion in aged mice, and increased apoptosis in these regions, recapitulating a hallmark of neurodegeneration. Quantitative proteomic analysis shows accumulation of endoplasmic reticulum (ER) proteins in KO mouse. Furthermore, we show that a defect in autophagy results in impaired ER turnover and ER stress. The unfolded protein response (UPR) is elevated through IRE1 and possibly other kinase signaling pathways, and eventually leads to neuronal apoptosis. Suppression of ER stress, or activation of autophagy through inhibition of mTOR pathway rescues neuronal death. Thus, our study not only provides mechanistic insights for BPAN, but also suggests that a defect in macroautophagy machinery leads to impairment in selective organelle autophagy.

cell biology↗

bioRxiv2017

Employing single-stranded DNA donors for the high-throughput production of conditional knockout alleles in mice

The International Mouse Phenotyping Consortium is generating null allele mice for every protein-coding gene in the genome and characterizing these mice to identify gene-phenotype associations. To test the feasibility of using CRISPR/Cas9 gene editing to generate conditional knockout mice for this large-scale resource, we employed Cas9-mediated homology driven repair (HDR) with short and long single-stranded oligodeoxynucleotides (ssODNs and lssODNs). Using pairs of guides and ssODNs donating loxP sites, we obtained putative conditional allele founder mice, harboring both loxP sites, for 23 of 30 genes targeted. LoxP sites integrated in cis in at least one F0 for 18 of 23 targeted genes. However, loxP sites were mutagenized in 4 of 18 in cis lines. HDR efficiency correlated with Cas9 cutting efficiency but was not influenced by ssODN homology arm symmetry. By contrast, using pairs of guides and a single lssODN to introduce a loxP-flanked exon, conditional allele founders were generated for all 4 genes targeted. Our studies demonstrate that Cas9-mediated HDR with pairs of ssODNs can generate conditional null alleles at many loci, but reveal inefficiencies when applied at scale. In contrast, lssODNs are amenable to high-throughput production of conditional alleles when they can be employed.

genetics↗