Biology subjects

Hao, C.

Publications and source records attributed to Hao, C..

26 records · Page 2Linked to original sources

bioRxiv2021

Miniature inverted-repeat transposable elements drive rapid microRNA diversification in angiosperms

MicroRNAs (miRNAs) are rapidly evolving endogenous small RNAs programing organism function and behavior. Although models for miRNA origination have been proposed based on sporadic cases, the genomic mechanisms driving swift diversification of the miRNA repertoires in plants remain elusive. Here, by comprehensively analyzing 20 phylogenetically representative plant species, we identified miniature inverted-repeat transposable elements (MITEs) as the predominant genomic sources for de novo miRNAs in angiosperms. Our data illustrated a transposition-transcription process whereby properly sized MITEs transposed into active genic regions could be converted into new miRNAs, termed MITE-miRNAs, in as few as 20 generations. We showed that this molecular domestication mechanism leads to a possible evolutionary arms race between the MITEs and the host genomes that rapidly and continuously changes the miRNA repertoires. We found that the MITE-miRNAs are selected for targeting genes associated with plant adaptation and habitat expansion, thereby constituting a genomic innovation potentially underlying angiosperm megadiversity.

plant biology↗

bioRxiv2021

The Copper Responsive Transcription Factor SPL7 Represses Key Abscisic Acid Biosynthetic Genes to Balance Growth and Drought Tolerance

Plants adapt to adverse environments by turning on defense against abiotic stresses, which is mainly orchestrated by the phytohormone abscisic acid (ABA). But how ABA homeostasis is modulated to balance growth and stress responses is still largely unknown. Here we report that prior treatment of Arabidopsis seedling with high copper retardates growth but enhances draught tolerance at later stages by modulating ABA accumulation. Subsequent genetic, physiological, transcriptomic, and molecular investigations revealed that the copper responsive transcription factor SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 7 (SPL7) is a strong regulator of ABA accumulation. We showed that SPL7 is destabilized by high copper and consistently suppresses genes encoding three key oxygenases in the ABA biosynthetic pathway of land plants via binding to the GTAC copper response motifs in their promoters. These results revealed a new mechanism whereby copper availability, inversely reflected by SPL7 abundance, modulates de novo ABA biosynthesis to balance growth and drought tolerance. One-sentence summaryHigh copper availability represses SPL7, releasing its suppression on key ABA biosynthetic genes and leading to increased ABA accumulation that inhibits growth but enhances drought tolerance.

plant biology↗

bioRxiv2020

Regulation of pancreatic fibrosis by acinar cell-derived exosomal miR-130a-3p via targeting of stellate cell PPAR-γ

As endogenous miRNA carriers,exosomes play a role in the pathophysiological process of various diseases. However, their functions and regulation mechanisms in pancreatic fibrosis remain unclear. In this study, an RNA microarray was used to detect differentially expressed exosomal miR-130a-3p in AR42J cells after taurolithocholate (TLC) treatment. mRNA-seq was used to screen the differentially expressed PPAR-{gamma} after pancreatic stellate cell (PSC) activation. Fluorescence labeling of exosomes and dynamic tracing showed that exosomes can fuse with the cell membrane of PSCs and transport miR-130a-3p into PSCs. A luciferase reporter gene assay was used to confirm that miR-130a can bind to PPAR-{gamma} to inhibit PPAR-{gamma} expression. In vitro and in vivo functional experiments were performed for gain-of-function studies and loss-of-function studies, respectively. These studies showed that acinar cell-derived exosomal miR-130a-3p promotes PSC activation and collagen formation through targeting of cellular PPAR-{gamma}. Knockdown of miR-130a-3p significantly improved pancreatic fibrosis. Notably, miR-130a-3p knockdown reduced serum levels of hyaluronic acid (HA) and {beta}-amylase and increased the C-peptide to protect endocrine and exocrine pancreatic functions and the function of endothelial cells. The exosomal miR-130a-3p/PPAR-{gamma} axis participates in the activation of PSCs and the mechanism of CP fibrosis, thus providing a potential new target for the treatment of chronic pancreatitis fibrosis.

cell biology↗

bioRxiv2020

The PIF1-MIR408-Plantacyanin Repression Cascade Regulates Light Dependent Seed Germination

Light-sensing seed germination is a vital process for the seed plants. A decisive event in light-induced germination is degradation of the central repressor PHYTOCHROME INTERACTING FACTOR1 (PIF1). It is also known that the balance between gibberellic acid (GA) and abscisic acid (ABA) critically controls germination. But the cellular mechanisms linking PIF1 turnover to hormonal rebalancing remain elusive. Here, employing far-red light-induced Arabidopsis seed germination as the experimental system, we identified Plantacyanin (PLC) as an inhibitor of germination, which is a storage vacuole-associated blue copper protein highly expressed in mature seed and rapidly silenced during germination. Molecular analyses showed that PIF1 directly binds to the MIR408 promoter and represses miR408 accumulation, which in turn post-transcriptionally modulates PLC abundance, thus forming the PIF1-MIR408-PLC repression cascade for translating PIF1 turnover to PLC turnover during early germination. Genetic analysis, RNA-sequencing, and hormone quantification revealed that PLC is necessary and sufficient to maintain the PIF1-mediated seed transcriptome and the low-GA-high-ABA state. Furthermore, we found that PLC domain organization and regulation by miR408 are conserved features in seed plants. These results unraveled a cellular mechanism whereby PIF1-relayed external light signals are converted through PLC-based copper mobilization into internal hormonal profiles for controlling seed germination.

plant biology↗

bioRxiv2020

Local Gazetteers Reveal Contrasting Patterns of Historical Changes between Apex Predators and Mesopredators in Eastern China

BackgroundHumans have been causing the sixth wave of mass extinction of biodiversity. The situation of predators, especially of carnivores, is a key indicator of biodiversity, and the mesopredator release is a typical phenomenon in ecosystem recess. Local gazetteers are a rich resource for historical biodiversity research. However there are obvious biases in previous studies focusing only on presence records and neglecting the absence records. I recollected and analyzed the records by fixed methods to research historical biodiversity change. MethodsInnovatively, this research used both presence and absence records from local gazetteers to reconstruct the distribution of 8 kinds of mammalian predators (i.e. large carnivores: tigers, leopards, and bears; medium-sized carnivores: wolves, foxes, civets, dholes, and mustelids) in eastern China from 1573C.E.(Common Era) to 1949C.E. (sorted into 4 periods). Then by utilizing statistics methods, e.g. Partial Least Squares Structural Equation Modeling(PLS-SEM), I analyzed the distribution changes(overall and sorted into 5 altitude groups), and the relation between carnivores and the influence from humans. Results & ConclusionsI reconstructed the specific distribution changes of the carnivores and found the changes match the mesopredator release phenomenon. Furthermore, I found the specific relation(e.g. trade-off effect) between carnivores and the influence of humans. Besides, I found that bears and civets may be potential members of the "Tigers - Leopards - Dholes" predator guild. ProspectsI have also collected records for other wild animals from local gazetteers in China. Based on this collection, I have built the Database of Wild Mammal Records in Chinese Local Gazetteers and am building the Database of Wild Bird Records in Chinese Local Gazetteers. I aim to continue relevant studies using these databases in the future.

ecology↗

bioRxiv2020

Universal NicE-seq for high resolution accessible chromatin profiling for formaldehyde fixed and FFPE tissues

Accessible chromatin plays a central role in gene expression and chromatin architecture. Current accessible chromatin approaches depend on limited digestion/cutting and pasting adaptors at the accessible DNA, thus requiring additional materials and time for optimization. Universal NicE-seq (UniNicE-seq) is an improved accessible chromatin profiling method that negate the optimization step and is suited to a variety of mammalian cells and tissues. Addition of 5-methyldeoxycytidine triphosphate during accessible chromatin labeling and an on-bead library making step substantially improved the signal to noise ratio while protecting the accessible regions from repeated nicking in cell lines, mouse T cells, mouse kidney, and human frozen tissue sections. We also demonstrate one tube UniNicE-seq for FFPE tissue section for direct NGS library preparation without sonication and DNA purification steps. These refinements allowed reliable mapping of accessible chromatin for high resolution genomic feature studies.

genetics↗

bioRxiv2020

BLOS1 mediates kinesin switch during endosomal recycling of LDL receptor

Low-density lipoprotein receptor (LDLR) in hepatocytes plays a key role in normal clearance of circulating LDL and in whole body cholesterol homeostasis. The trafficking of LDLR is highly regulated in clathrin-dependent endocytosis, endosomal recycling and lysosomal degradation. Current studies have been focusing on its endocytosis and degradation. However, the detailed molecular and cellular mechanisms underlying its endosomal recycling are largely unknown. We found that BLOS1, a shared subunit of BLOC-1 and BORC, is involved in LDLR endosomal recycling. Loss of BLOS1 leads to less membrane LDLR and impairs LDL clearance from plasma in hepatocyte-specific BLOS1 knockout mice. BLOS1 interacts with kinesin-3, and that BLOS1 acts as a new adaptor for kinesin-2 to coordinate kinesin-3 and kinesin-2 during the long-range transport of recycling endosomes (REs) to plasma membrane along microtubule tracks to overcome hurdles at microtubule intersections. These findings provide new insights into REs anterograde transport and the pathogenesis of dyslipidemia.

cell biology↗

bioRxiv2018

High glucose-induced ubiquitylation of G6PD leads to the injury of podocyte

Oxidative stress contributes substantially to podocyte injury in diabetic kidney disease. The mechanism of hyperglycemia-induced oxidative stress in podocytes is not fully understood. Glucose-6-phosphate dehydrogenase is critical in maintaining NADPH, an important cofactor for antioxidant system. Here, we hypothesized that high glucose induces ubiquitylation and degradation of G6PD, which injures podocytes by reactive oxygen species (ROS) accumulation. We found that both G6PD protein expression and G6PD activity was decreased in kidneys of both diabetic patients and diabetic rodents. Overexpressing G6PD reversed redox imbalance and podocyte apoptosis induced by high glucose and palmitate. Inhibition of G6PD induced podocyte apoptosis. In G6PD deficient mice, podocyte apoptosis was also largely increased. High glucose had no effect on G6PD mRNA level but it caused decreased G6PD protein expression, which was mediated by the ubiquitin proteasome pathway. Furthermore, von Hippel-Lindau (VHL), an E3 ubiquitin ligase subunit, directly bound to G6PD and degraded G6PD through ubiquitylating G6PD on lysine residues 366/403. Our data suggest that high glucose induces ubiquitylation of G6PD by VHL, which leads to ROS accumulation and podocyte injury.

cell biology↗