Biology subjects

Ding, P.

Publications and source records attributed to Ding, P..

29 records · Page 2Linked to original sources

bioRxiv2021

Network pharmacology and chemoproteomics unveil the mechanism of Total Flavonoid Aglycones Extract inhibiting EMT in A549 cell line

Non-small cell lung cancer (NSCLC) is a worldwide disease with high morbidity and mortality, which is most derived from its metastasis. Some researches show that the epithelial-mesenchymal transition (EMT) process promotes lung cancer cells migration and invasion, leading to NSCLC metastasis. Total Flavonoid Aglycones Extract (TFAE) isolated from Scutellaria baicalensis was reported to inhibit tumor growth and induce apoptosis. In this study, we found that baicalein, wogonin, and oroxylin-A were the active compounds of TFAE. After reconstructing with these three compounds (baicalein (65.8%), wogonin (21.2%), and oroxylin-A (13.0%)), the reconstructed TFAE (reTFAE) present inhibitory effect on the EMT process of A549 cells. Then, bioinformatic technology was employed to elucidate the potential pharmacodynamic mechanism network of reTFAE. We identified the relationship between reTFAE and PI3K/Akt signaling pathways, with TWIST1 as the key protein. LY294002, the inhibitor of PI3K/Akt signaling pathway, and knock-down TWIST1 could significantly enhance the efficacy of reTFAE, with increasing expression of epithelial markers and decreasing expression of mesenchymal markers in A549 cells at the same time. Furthermore, stable isotope dimethyl-labeled proteomics technology was conducted to complement the follow-up mechanism that the EMT-inhibition process may be realized through glycolysis pathway. In conclusion, we claim that TWIST1-targeted flavonoids could provide a new strategy to inhibit EMT progress for the treatment of NSCLC.

pharmacology and toxicology↗

bioRxiv2020

Chromatin accessibility landscapes activated by cell surface and intracellular immune receptors

Activation of cell Surface and Intracellular Receptor-Mediated Immunity (SRMI and IRMI) results in rapid transcriptional reprogramming that underpins disease resistance. However, the mechanisms by which SRMI and IRMI lead to transcriptional changes are not clear. Here, we combine RNA-seq and ATAC-seq to define changes in gene expression and chromatin accessibility; both SRMI and IRMI increase chromatin accessibility at induced defense genes. Analysis of ATAC-seq and RNA-seq data combined with publicly available information on transcription factor DNA-binding motifs enabled comparison of individual gene regulatory networks activated by SRMI and IRMI, and by both. These results and analyses reveal overlapping and conserved transcriptional regulatory mechanism between the two immune systems.

plant biology↗

bioRxiv2020

Single-cell screening of SARS-CoV-2 target cells in pets, livestock, poultry and wildlife

A few animals have been suspected to be intermediate hosts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a large-scale single-cell screening of SARS-CoV-2 target cells on a wide variety of animals is missing. Here, we constructed the single-cell atlas for 11 representative species in pets, livestock, poultry, and wildlife. Notably, the proportion of SARS-CoV-2 target cells in cat was found considerably higher than other species we investigated and SARS-CoV-2 target cells were detected in multiple cell types of domestic pig, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic and keep pigs under surveillance for the possibility of becoming intermediate hosts in future coronavirus outbreak. Furthermore, we screened the expression patterns of receptors for 144 viruses, resulting in a comprehensive atlas of virus target cells. Taken together, our work provides a novel and fundamental strategy to screen virus target cells and susceptible species, based on single-cell transcriptomes we generated for domesticated animals and wildlife, which could function as a valuable resource for controlling current pandemics and serve as an early warning system for coping with future infectious disease threats.

cell biology↗

bioRxiv2020

Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease.

The kidney has a limited capacity to repair following injury, however, the endogenous reparative pathways are not well understood. Here we employ integrated droplet- and plate-based scRNA-seq in the murine reversible unilateral ureteric obstruction model to dissect the transcriptomic landscape at the single cell level during renal injury and resolution of fibrosis. We generate a comprehensive catalogue of the changes induced during injury and repair, revealing significant myeloid cell heterogeneity, which would not have been identifiable by conventional flow cytometry. We identify new markers for the myeloid populations within the kidney as well as identification of novel subsets including an Arg1+ monocyte population specific to early injury and a Mmp12+ macrophage subset exclusive to repair. Finally, using paired blood exchange to track circulating immune cells, we confirm that monocytes are recruited to the kidney early after injury and are the source of Ccr2+ macrophages that accumulate in late injury. Our data demonstrate the utility of complementary technologies to identify novel myeloid subtypes that may represent therapeutic targets to inhibit progression or promote regression of kidney disease.

immunology↗

bioRxiv2020

Mutual Potentiation of Plant Immunity by Cell-surface and Intracellular Receptors

The plant immune system involves cell-surface receptors that detect intercellular pathogen-derived molecules, and intracellular receptors that activate immunity upon detection of pathogen-secreted effectors that act inside the plant cell. Surface receptor-mediated immunity has been extensively studied but in authentic interactions between plants and microbial pathogens, its presence impedes study of intracellular receptor-mediated immunity alone. How these two immune pathways interact is poorly understood. Here, we reveal mutual potentiation between these two recognition-dependent defense pathways. Recognition by surface receptors activates multiple protein kinases and NADPH oxidases, whereas intracellular receptors primarily elevate abundance of these proteins. Reciprocally, the intracellular receptor-dependent hypersensitive cell death response is strongly enhanced by activation of surface receptors. Activation of either immune system alone is insufficient to provide effective resistance against Pseudomonas syringae. Thus, immune pathways activated by cell-surface and intracellular receptors mutually potentiate to activate strong defense that thwarts pathogens. By studying the activation of intracellular receptors in the absence of surface receptor-mediated immunity, we have dissected the relationship between the two distinct immune systems. These findings reshape our understanding of plant immunity and have broad implications for crop improvement.

plant biology↗

bioRxiv2020

Single cell atlas of trisomy 21 cerebral cortex

Down syndrome (DS) is one of the most common human birth defects caused by trisomy 21 (T21), leading to a variety of cognitive impairments. The cellular composition of human brain has been explored using single cell RNA sequencing in both physiological and pathological conditions. However, the cellular heterogeneity of human brain with chromosome aneuploidy is largely unknown. Here, we profiled the transcriptome of 36046 cells in cerebral cortex of T21 human fetus, covering frontal lobe, parietal lobe, occipital lobe and temporal lobe. Intriguingly, we detected several genes positively associated with neurons maturation was dysregulated in T21 frontal cortex (HIC2, POU2F2, ZGLP1 and FOXK1). To share, explore and utilized the data resources of T21 cerebral cortex, we developed a comprehensive platform named T21atlas, composing of two functional modules (T21cluster and T21talk). Overall, our study provides, as far as we know, the first single cell atlas for T21 cerebral cortex, which could promote our understanding of the molecular mechanism of DS at an unprecedented resolution and could potentially facilitate the development of novel clinical therapeutics against T21.

neuroscience↗

bioRxiv2019

High-resolution Expression Profiling of Selected Gene Sets during Plant Immune Activation

Sequence capture followed by next-generation sequencing has broad applications in cost-effective exploration of biological processes at high resolution [1, 2]. Genome-wide RNA sequencing (RNA-seq) over a time course can reveal the dynamics of differential gene expression. However, in many cases, only a limited set of genes are of interest, and are repeatedly used as markers for certain biological processes. Sequence capture can help generate high-resolution quantitative datasets to assess changes in abundance of selected genes. We previously used sequence capture to accelerate Resistance gene cloning [1, 3, 4], investigate immune receptor gene diversity [5] and investigate pathogen diversity and evolution [6, 7].\n\nThe plant immune system involves detection of pathogens via both cell-surface and intracellular receptors. Both receptor classes can induce transcriptional reprogramming that elevates disease resistance [8]. To assess differential gene expression during plant immunity, we developed and deployed quantitative sequence capture (CAP-I). We designed and synthesized biotinylated single-strand RNA bait libraries targeted to a subset of defense genes, and generated sequence capture data from 99 RNA-seq libraries. We built a data processing pipeline to quantify the RNA-CAP-I-seq data, and visualize differential gene expression. Sequence capture in combination with quantitative RNA-seq enabled cost-effective assessment of the expression profile of a specified subset of genes. Quantitative sequence capture is not limited to RNA-seq or any specific organism and can potentially be incorporated into automated platforms for high-throughput sequencing.

plant biology↗

bioRxiv2019

Estradiol-inducible AvrRps4 expression reveals distinct properties of TIR-NLR-mediated effector-triggered immunity

Plant nucleotide-binding domain, leucine-rich repeat receptor (NLR) proteins play important roles in recognition of pathogen-derived effectors. However, the mechanism by which plant NLRs activate immunity is still largely unknown. The paired Arabidopsis NLRs RRS1-R and RPS4, that confer recognition of bacterial effectors AvrRps4 and PopP2, are well studied, but how the RRS1/RPS4 complex activates early immediate downstream responses upon effector detection is still poorly understood. To study RRS1/RPS4 responses without the influence of cell-surface receptor immune pathways, we generated an Arabidopsis line with inducible expression of effector AvrRps4. Induction does not lead to hypersensitive cell death response (HR) but can induce electrolyte leakage, which often correlates with plant cell death. Activation of RRS1 and RPS4 without pathogens cannot activate mitogen-associated protein kinase cascades, but still activates upregulation of defense genes, and therefore resistance against bacteria.\n\nHighlightInducible expression of AvrRps4 activates RRS1/RPS4-mediated effector-triggered immunity without the presence of pathogens, allowing us to characterise downstream immune responses triggered by TIR-NLRs without cell-surface receptor-mediated immunity.

plant biology↗

bioRxiv2019

PI3K/AKT inhibition in tumor propagating cells of DLBCL reverses R-CHOP resistance by destabilizing SOX2

Drug resistance is a major obstacle for the success of conventional anticancer therapy, and the development of drug resistance is at least partly attributed to tumor propagating cells (TPCs). Up to one-third of diffuse large B cell lymphoma (DLBCL) patients eventually develop resistance to R-CHOP regimen. We found that the TPC proportion was remarkably increased in resistant germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL subtypes. Elevated SOX2 was the determinant for resistance development, and SOX2 was phosphorylated by activated PI3K/AKT1 signaling, thus preventing ubiquitin-mediated SOX2 degradation. Furthermore, multiple factors, including BCR, integrins, chemokines and FGFR1/2 signaling, regulated PI3K/AKT1 activation. CDK6 in the GCB subtype and FGFR1/2 in the ABC subtype were SOX2 targets in the PI3K/AKT1 pathway. Chemical inhibition of PI3K/AKT1 in both subtypes, CDK6 in the GCB subtype, and FGFR1/2 in the ABC subtype significantly enhanced the susceptibility of resistant cells to CHO treatment. More importantly, PI3K and FGFR1/2 inhibitors but not a CDK6 inhibitor effectively suppressed the tumor growth of R-CHO-resistant DLBCL cells, most likely by converting TPCs to chemo-sensitive differentiated cells. Therefore, this pro-differentiation therapy against TPCs warrants further study in clinical trials for the treatment of resistant DLBCL.

cancer biology↗

bioRxiv2019

Sing cell RNA-seq reveals cellular diversity and developmental characteristics of human infant retina

Retina, located in the innermost layer of the eye of human, holds the decisive role in visual perception. Dissecting the heterogeneity of retina is essential for understanding the mechanism of vision formation and even the development of central nervous system (CNS). Here, we performed single cell RNA-seq, analyzed 57,832 cells from human infant donors, resulting in 20 distinct clusters representing major cell types in retina: rod photoreceptors, cone photoreceptors, bipolar cells, horizontal cells, amacrine cells, Muller glia cells and microglia. We next constructed extensive networks of intercellular communication and identified ligand-receptor interactions playing crucial roles in regulating neural cell development and immune homeostasis in retina. Though re-clustering, we identified known subtypes in cone PRs and additional unreported subpopulations and corresponding markers in rod PRs as well as bipolar cells. Additionally, we linked inherited retinal disease to certain cell subtypes or subpopulations through enrichment analysis. Intriguingly, we found that status and functions of photoreceptors changed drastically between early and late retina. Overall, our study offers the first retinal cell atlas in human infants, dissecting the heterogeneity of retina and identifying the key molecules in the developmental process, which provides an important resource that will pave the way for retina development mechanism research and regenerative medicine concerning retinal biology.

cell biology↗

bioRxiv2018

Aerobic removal of microcystin-LR by a novel native effective bacterial community designated as YFMCD4 isolated from Lake Taihu

Microcystins (MCs) are a group of monocyclic heptapeptide hepatotoxins produced by species of cyanobacteria. MC-LR is the most toxic and frequently detected MCs variant in water, which poses a great threat to the natural ecosystem and public health. Its important to seek environment-friendly and cost-efficient methods to remove MC-LR. To investigate the MC-degrading capacities of a novel indigenous bacterial community designated as YFMCD4 and the influence of environmental factors including various temperatures, MC concentrations and pH on the MC-degrading activities, the concentration of MC-LR was measured by high performance liquid chromatography. In addition, the MC-degrading mechanism containing the degradation pathway and products of YFMCD4 was studied using HPLC coupled with an ultra-high resolution LTQ Orbitrap Velos Pro ETD mass spectrometry equipped with electrospray ionization interface. The data showed MC-LR can be removed at the maximum rate of 0.5 {micro}g/(ml{middle dot}h) by YFMCD4 containing Alcaligenes faecalis and Stenotrophomonas acidaminiohila. The MC-degrading rates of YFMCD4 were significantly affected by different temperatures, pH and MC-LR concentrations. Two intermediates of a tetrapeptide and Adda appeared in the degradation process. These results illustrate that the novel bacterial community YFMCD4 can remove MC-LR effectively and completely, which indicates YFMCD4 possesses a significant potential to be used in bioremediation of water bodies contaminated by MC-LR.

ecology↗