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Xu, D.

Publications and source records attributed to Xu, D..

At least 199 records · Page 11Linked to original sources

Assessing deep learning algorithms in cis-regulatory motif finding based on genomic sequencing data

Cis-regulatory motif finding is a crucial step in the detection of gene regulatory mechanisms using genomic data. Deep learning (DL) models have been utilized to denovoly identify motifs, and have been proven to outperform traditional methods. By 2020, twenty DL models have been developed to identify DNA and RNA motifs with diverse framework designs and implementation styles. Hence, it is beneficial to systematically compare their performances, which can facilitate researchers in selecting the appropriate tools for their motif analyses. Here, we carried out an in-depth assessment of the 20 models utilizing 1,043 genomic sequencing datasets, including 690 ENCODE ChIP-Seq, 126 cancer ChIP-Seq, 172 single-cell cleavages under targets and release using a nuclease, and 55 RNA CLIP-Seq. Four metrics were designed and investigated, including the accuracy of motif finding, the performance of DNA/RNA sequence classification, algorithm scalability, and tool usability. The assessment results demonstrated the high complementarity of the existing models, and it was determined that the most suitable model should primarily depend on the data size and type as well as the model outputs. A webserver was developed to allow efficient access of the identified motifs and effective utilization of high-performing DL models.

bioinformatics↗

A body map of somatic mutagenesis in morphologically normal human tissues

Somatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each), mostly from the epithelia, of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although with variable extent, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes like SBS22 were found in different tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In epithelial tissues from esophagus and cardia, macroscopic somatic clones expanded to several millimeters were frequently seen, whereas in tissues from colon, rectum, and duodenum somatic clones were microscopic in size and evolved independently. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.

genomics↗

SPDE: A Multi-functional Software for Sequence Processing and Data Extraction

Efficiently extracting information from biological big data can be a huge challenge for people (especially those who lack programming skills). We developed Sequence Processing and Data Extraction (SPDE) as an integrated tool for sequence processing and data extraction for gene family and omics analyses. Currently, SPDE has seven modules comprising 100 basic functions that range from single gene processing (e.g., translation, reverse complement, and primer design) to genome information extraction. All SPDE functions can be used without the need for programming or command lines. The SPDE interface has enough prompt information to help users run SPDE without barriers. In addition to its own functions, SPDE also incorporates the publicly available analyses tools (such as, NCBI-blast, HMMER, Primer3 and SAMtools), thereby making SPDE a comprehensive bioinformatics platform for big biological data analysis. AvailabilitySPDE was built using Python and can be run on 32-bit, 64-bit Windows and macOS systems. It is an open-source software that can be downloaded from https://github.com/simon19891216/SPDEv1.2.git. Contactxudongzhuanyong@163.com

bioinformatics↗

Candidate Explorer: a tool for discovery, evaluation, and display of mutations causing significant immune phenotypes

When applied to immunity, forward genetic studies use meiotic mapping to provide strong statistical evidence that a particular mutation is causative of a particular immune phenotype. Notwithstanding this, co-segregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the selection of authentic causative mutations using a machine learning software tool, Candidate Explorer (CE), which integrates 65 data features into a single numeric score, mathematically convertible to the likelihood of verification of any putative mutation-phenotype association. CE has identified most genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus. The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

genetics↗

Inductive Inference of Gene Regulatory Network Using Supervised and Semi-supervised Graph Neural Networks

Discovering gene regulatory relationships and reconstructing gene regulatory networks (GRN) based on gene expression data is a classical, long-standing computational challenge in bioinformatics. Computationally inferring a possible regulatory relationship between two genes can be formulated as a link prediction problem between two nodes in a graph. Graph neural network (GNN) provides an opportunity to construct GRN by integrating topological neighbor propagation through the whole gene network. We propose an end-to-end gene regulatory graph neural network (GRGNN) approach to reconstruct GRNs from scratch utilizing the gene expression data, in both a supervised and a semi-supervised framework. To get better inductive generalization capability, GRN inference is formulated as a graph classification problem, to distinguish whether a subgraph centered at two nodes contains the link between the two nodes. A linked pair between a transcription factor (TF) and a target gene, and their neighbors are labeled as a positive subgraph, while an unlinked TF and target gene pair and their neighbors are labeled as a negative subgraph. A GNN model is constructed with node features from both explicit gene expression and graph embedding. We demonstrate a noisy starting graph structure built from partial information, such as Pearsons correlation coefficient and mutual information can help guide the GRN inference through an appropriate ensemble technique. Furthermore, a semi-supervised scheme is implemented to increase the quality of the classifier. When compared with established methods, GRGNN achieved state-of-the-art performance on the DREAM5 GRN inference benchmarks. GRGNN is publicly available at https://github.com/juexinwang/GRGNN. HighlightsO_LIWe present a novel formulation of graph classification in inferring gene regulatory relationships from gene expression and graph embedding. C_LIO_LIOur method leverages a powerful framework, gene regulatory graph neural network (GRGNN), which is flexible and powerful to ensemble statistical powers from a number of heuristic skeletons. C_LIO_LIOur results show GRGRNN outperforms previous supervised and unsupervised methods inductively on benchmarks. C_LIO_LIGRGNN can be interpreted and explained following the biological network motif hypothesis in gene regulatory networks. C_LI

bioinformatics↗

Casein Kinase 1G2 Suppresses Necroptosis-Promoted Testis Aging by Inhibiting Receptor-Interacting Kinase 3

Casein kinases are a large family of intracellular serine/threonine kinases that control a variety of cellular signaling functions. Here we report that a member of casein kinase 1 family, casein kinase 1G2, CSNK1G2, binds and inhibits the activation of receptor-interacting kinase 3, RIP3, thereby attenuating RIP3-mediated necroptosis. The binding of CSNK1G2 to RIP3 is triggered by auto-phosphorylation at serine 211/threonine 215 sites in its C-terminal domain. CSNK1G2-knockout mice showed significantly enhanced necroptosis response and pre-maturing aging of their testis, a phenotype that was rescued by either double knockout of the RIP3 gene or feeding the animal with a RIP1 kinase inhibitor-containing diet. Moreover, CSNK1G2 is also co-expressed with RIP3 in human testis, and the necroptosis activation marker phospho-MLKL was observed in the testis of old (>80) but not young men, indicating that the testis-aging program carried out by the RIP3-mediated and CSNK1G2-attenuated necroptosis is evolutionarily conserved between mice and men.

cell biology↗

Prime editing primarily induces undesired outcomes in mice

Genome editing has transformed biomedical science, but is still unpredictable and often induces undesired outcomes. Prime editing (PE) is a promising new approach due to its proposed flexibility and ability to avoid unwanted indels. Here, we show highly efficient PE-mediated genome editing in mammalian zygotes. Utilizing chemically modified guideRNAs, PE efficiently introduced 10 targeted modifications including substitutions, deletions, and insertions across 6 genes in mouse embryos. However, we unexpectedly observed a high frequency of undesired outcomes such as large deletions and found that these occurred more often than pure intended edits across all of the edits/genes. We show that undesired outcomes result from the double-nicking PE3 strategy, but that omission of the second nick largely ablates PE function. However, sequential double-nicking with PE3b, which is only applicable to a fraction of edits, eliminated undesired outcomes. Overall, our findings demonstrate the promising potential of PE for predictable, flexible, and highly efficient in vivo genome editing, but highlight the need for improved variations of PE before it is ready for widespread use.

molecular biology↗

scGNN: a novel graph neural network framework for single-cell RNA-Seq analyses

Single-cell RNA-sequencing (scRNA-Seq) is widely used to reveal the heterogeneity and dynamics of tissues, organisms, and complex diseases, but its analyses still suffer from multiple grand challenges, including the sequencing sparsity and complex differential patterns in gene expression. We introduce the scGNN (single-cell graph neural network) to provide a hypothesis-free deep learning framework for scRNA-Seq analyses. This framework formulates and aggregates cell-cell relationships with graph neural networks and models heterogeneous gene expression patterns using a left-truncated mixture Gaussian model. scGNN integrates three iterative multi-modal autoencoders and outperforms existing tools for gene imputation and cell clustering on four benchmark scRNA-Seq datasets. In an Alzheimers disease study with 13,214 single nuclei from postmortem brain tissues, scGNN successfully illustrated disease-related neural development and the differential mechanism. scGNN provides an effective representation of gene expression and cell-cell relationships. It is also a novel and powerful framework that can be applied to scRNA-Seq analyses.

bioinformatics↗

Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition

Blood pH is tightly regulated between 7.35-7.45, with values below 7.3 during sepsis being associated with lactic acidosis, low serum zinc, and release of proinflammatory HMGB1 from activated and/or necrotic cells. Using an ex vivo whole blood system to model lactic acidosis, we show that while HMGB1 does not engage leukocyte receptors at physiological pH, lowering pH with lactic acid facilitates binding. At normal pH, micromolar zinc supports plasma sialoglycoprotein binding by HMGB1, which is markedly reduced when pH is adjusted with lactic acid to sepsis levels. Glycan array studies confirmed zinc and pH-dependent HMGB1 binding to sialoglycans typical of plasma glycoproteins. Thus, proinflammatory effects of HMGB1 are suppressed via plasma sialoglycoproteins until drops in pH and zinc release HMGB1 to trigger downstream immune activation. Significance StatementHMGB1 sequestered by plasma sialoglycoproteins at physiological pH is released when pH and zinc concentrations fall in sepsis.

immunology↗

Global reinforcement of DNA methylation through enhancement of RNA-directed DNA methylation ensures sexual reproduction in rice

DNA methylation is an important epigenetic mark that regulates the expression of genes and transposons. RNA-directed DNA methylation (RdDM) is the main molecular pathway responsible for de novo DNA methylation in plants. In Arabidopsis, however, mutations in RdDM genes cause no visible developmental defects, which raising the question of the biological significance of RdDM in plant development. Here, we isolated and cloned Five Elements Mountain 1 (FEM1), which encodes an RNA-dependent RNA polymerase. Mutation in FEM1 substantially decreased genome-wide CHH methylation levels and abolished the accumulation of 24-nt small interfering RNAs. Moreover, male and female reproductive development was disturbed, which led to the sterility of fem1 mutants. In wild-type (WT) plants but not in fem1 mutants, genome-wide CHH DNA methylation levels were greater in panicles, stamens, and pistils than in seedlings. The global increase of methylation in reproductive organs of the WT was attributed to enhancement of RdDM activity including FEM1 activity. More than half of all encoding genes in the rice genome overlapped with hypermethylated regions in the sexual organs of the WT, and many of them appear to be directly regulated by an increase in DNA methylation.Our results demonstrate that a global increase of DNA methylation through enhancement of RdDM activity in reproductive organs ensures sexual reproduction of rice.View Full Text

plant biology↗

Red-light is an environmental effector for mutualism between begomovirus and its vector whitefly

Environments such as light condition influence the spread of infectious diseases by affecting insect vector behavior. However, whether and how light affects the host defense which further affect insect preference and performance, remains unclear, nor has been demonstrated how pathogens co-adapt light condition to facilitate vector transmission. We previously showed that begomoviral βC1 inhibits MYC2-mediated jasmonate signaling to establish plant-dependent mutualism with its insect vector. Here we show red-light as an environmental catalyzer to promote mutualism of whitefly-begomovirus by stabilizing βC1, which interacts with PHYTOCHROME-INTERACTING FACTORS (PIFs) transcription factors. PIFs positively control plant defenses against whitefly by directly binding to the promoter of terpene synthase genes and promoting their transcription. Moreover, PIFs integrates light and jasmonate signaling by interaction with MYC2, and co-regulation the transcription of terpene synthase genes. However, begomovirus encoded βC1 inhibit PIFs’ and MYC2’ transcriptional activity via disturbing their dimerization, thereby impairing plant defenses against whitefly-transmitted begomoviruses. Our results thus describe how a viral pathogen hijacks host light signaling to enhance the mutualistic relationship with its insect vector.Author summary Climate change is driving disease rapidly spread, esp. for global distribution of insect-borne diseases. This paper reports red-light as an environmental factor to promote insect vector olfactory orientation behavior and increase viral disease transmission. Plant virus adapts the supplemental red lighting practice in modern agricultural greenhouse production under protection, therefore enhancing disease spreading globally.View Full Text

plant biology↗

Population Pharmacokinetics of an Anti-PD-1 Antibody Camrelizumab in Patients with Multiple tumor types and model informed dosing strategy

Objective Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been approved for the treatment of relapsed or refractory classical Hodgkin lymphoma. The aim of this study was to perform a population pharmacokinetics (PK) analysis of camrelizumab to quantify the impact of patient characteristics on PK and to investigate the appropriateness of flat dose in the dosing regimen.Methods A total of 3298 camrelizumab concentrations from 133 patients from four studies were analyzed using nonlinear mixed effects modeling. Covariate model building was conducted using stepwise forward addition and backward elimination. Monte Carlo simulation was conducted to compare exposures of 200 mg and 3 mg/kg every 2-week regimens.Results The PK of camrelizumab were adequately described by a two-compartment model with parallel linear and nonlinear clearances. Baseline albumin had significant effects on linear clearance, and weight had effects on inter-compartmental clearance. Moreover, 200 mg and 3 mg/kg regimens provide similar exposure distributions with no advantage to either dosing approach.Conclusion Population PK analysis provided an integrated evaluation of the impact of albumin and weight on the PK of camrelizumab. It also provided evidence that neither the flat-dose nor the weight-based dose regimen was advantageous over the other for most patients with tumors.Competing Interest StatementThis study was sponsored by Jiangsu Hengrui Medicine Co. Ltd. Guang-li Ma, Da Xu and Yu-ya Wang are employees of Jiangsu Hengrui Medicine Co. Ltd.AbbreviationsAICAkaike’s information criterion;AUCarea under the concentration-time curve;AUCsssteady-state area under the concentration-time curve;BSVBetween-subject variability;Ccamrelizumab concentration;C1concentration of central compartment;Caverage,sssteady-state average concentration;CLclearance;CLlinearclearance of linear elimination;Cmax,sssteady-state peak concentration;CLnonlinearclearance of nonlinear elimination;Cmin,sssteady-state trough concentration;CWRESconditional weighted residuals;DVobserved concentration;IPREDindividual predicted concentrations;k0infusion rate;k23elimination rate from central compartment to peripheral compartment;k32elimination rate from peripheral compartment to central compartment;klinearlinear elimination rate;knonlinearnonlinear elimination rate;KmMichaelis–Menten constant;mAbmonoclonal antibody;NONMEMnonlinear mixed effect modeling;PD-1programmed cell death 1 receptor;PKpharmacokinetics;PREDpopulation predicted concentration;Qinter-compartmental clearance;Q2Wevery 2 weeks;Vmmaximum elimination rate;VPCvisual predictive check;V1distribution volume of central compartment;V2distribution volume of peripheral compartment;WBCwhite blood cell.View Full Text

cancer biology↗

Identification of Candidate COVID-19 Therapeutics using hPSC-derived Lung Organoids

Summary ParagraphThe SARS-CoV-2 virus has caused already over 3.5 million COVID-19 cases and 250,000 deaths globally. There is an urgent need to create novel models to study SARS-CoV-2 using human disease-relevant cells to understand key features of virus biology and facilitate drug screening. As primary SARS-CoV-2 infection is respiratory-based, we developed a lung organoid model using human pluripotent stem cells (hPSCs) that could be adapted for drug screens. The lung organoids, particularly aveolar type II cells, express ACE2 and are permissive to SARS-CoV-2 infection. Transcriptomic analysis following SARS-CoV-2 infection revealed a robust induction of chemokines and cytokines with little type I/III interferon signaling, similar to that observed amongst human COVID-19 pulmonary infections. We performed a high throughput screen using hPSC-derived lung organoids and identified FDA-approved drug candidates, including imatinib and mycophenolic acid, as inhibitors of SARS-CoV-2 entry. Pre- or post-treatment with these drugs at physiologically relevant levels decreased SARS-CoV-2 infection of hPSC-derived lung organoids. Together, these data demonstrate that hPSC-derived lung cells infected by SARS-CoV-2 can model human COVID-19 disease and provide a valuable resource to screen for FDA-approved drugs that might be repurposed and should be considered for COVID-19 clinical trials.

microbiology↗

Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids

Summary ParagraphThe current COVID-19 pandemic is caused by SARS-coronavirus 2 (SARS-CoV-2). There are currently no therapeutic options for mitigating this disease due to lack of a vaccine and limited knowledge of SARS-CoV-2 biology. As a result, there is an urgent need to create new disease models to study SARS-CoV-2 biology and to screen for therapeutics using human disease-relevant tissues. COVID-19 patients typically present with respiratory symptoms including cough, dyspnea, and respiratory distress, but nearly 25% of patients have gastrointestinal indications including anorexia, diarrhea, vomiting, and abdominal pain. Moreover, these symptoms are associated with worse COVID-19 outcomes1. Here, we report using human pluripotent stem cell-derived colonic organoids (hPSC-COs) to explore the permissiveness of colonic cell types to SARS-CoV-2 infection. Single cell RNA-seq and immunostaining showed that the putative viral entry receptor ACE2 is expressed in multiple hESC-derived colonic cell types, but highly enriched in enterocytes. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. We used hPSC-derived COs in a high throughput platform to screen 1280 FDA-approved drugs against viral infection. Mycophenolic acid and quinacrine dihydrochloride were found to block the infection of SARS-CoV-2 pseudo-entry virus in COs both in vitro and in vivo, and confirmed to block infection of SARS-CoV-2 virus. This study established both in vitro and in vivo organoid models to investigate infection of SARS-CoV-2 disease-relevant human colonic cell types and identified drugs that blocks SARS-CoV-2 infection, suitable for rapid clinical testing.

microbiology↗

Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets.

molecular biology↗

MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes

The efficacy of aminolevulinic acid (5-ALA)-based photodynamic diagnosis (5-ALA-PDD) and photodynamic therapy (5-ALA-PDT) is dependent on the 5-ALA-induced cancer-specific accumulation of protoporphyrin IX (PpIX). We previously reported that inhibition of oncogenic Ras/MEK increases PpIX accumulation in cancer cells by reducing PpIX efflux through ATP-binding cassette sub-family B member 1 (ABCB1) as well as PpIX conversion to heme by ferrochelatase (FECH). Here, we sought to identify the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation via ABCB1 and FECH. First, we demonstrated that Ras/MEK activation reduced PpIX accumulation in RasV12-transformed NIH3T3 cells and HRAS transgenic mice. Knockdown of p90 ribosomal S6 kinases (RSK) 2, 3, or 4 increased PpIX accumulation in the RasV12-transformed NIH3T3 cells. Further, treatment with an RSK inhibitor reduced ABCB1 expression and increased PpIX accumulation. Moreover, HIF-1 expression was reduced when the RasV12-transformed NIH3T3 cells were treated with a MEK inhibitor, demonstrating that HIF-1 is a downstream element of MEK. HIF-1 inhibition decreased the activity of FECH and increased PpIX accumulation. Finally, we demonstrated the involvement of RSKs and HIF-1 in the regulation of PpIX accumulation in human cancer cell lines (DLD-1, SNB-75, Hs 578T, and MDA MB 231). These results demonstrate that the RSK-ABCB1 and HIF-1-FECH axes are the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation.

cancer biology↗

Kruppel-Like Factor 14 Improves Cardiac Function After Myocardial Infarction

BackgroundReversal of heart failure after myocardial infarction (MI) remains a global challenge. The goal of a clinical physician is to prevent heart failure immediately following the infarct. Since traditional strategies are only partially helpful for improving cardiac function, there is an urgency to identify novel approaches to maintain cardiac function. ObjectivesThe aim of this study was to determine the role of Kruppel-Like Factor 14 (KLF14) in the heart post-MI. Methods and ResultsWild-type and KLF14 overexpression mice were subjected to MI. At four weeks following MI, the infarct size was significantly reduced, left ventricular fraction shortening was significantly preserved, and left ventricular chamber dilation was attenuated in the KLF14 overexpression group. Transmission electron microscopy studies revealed striking evidence of decreased mitochondrial damage in the KLF14 overexpression myocardium following MI. To gain insight into the underlying relationship between KLF14 and mitochondria, we examined a broad array of genes involved in mitochondrial function and found that KLF14 overexpression was involved in the decreased apoptosis of mitochondria induced by H2O2. This beneficial effect was associated with increased levels of PGC-1. ConclusionsThese results demonstrate that KLF14 plays a critical protective role in the heart after MI by regulating mitochondrial function, which may be achieved by regulating PGC-1.

pathology↗

Traceback of Core Transcription Factors for Soybean Root Growth Maintenance under Water Deficit

Some crops inhibit shoot growth but maintain root growth under water-deficit conditions. Unraveling the molecular mechanisms of root plasticity under water deficit conditions in plants remains a major challenge. We developed an efficient platform for identifying core transcription factors (TFs) that collectively regulate each other and/or themselves in response to water stress, and exploring their interconnected regulatory circuitry involved in root growth maintenance under water deficit in soybean. We performed multi-species phylogenetic footprinting combined with spatial-temporal transcriptome analysis of soybean (Glycine max) roots under water deficit to identify conserved motifs that function in the water-stress response. Using these functional conserved cis-motifs, we applied a new approach to trace back motifs-associated core TFs ingroup as signal mediators, which mediate signaling between abiotic and endogenous stimuli. We integrated a co-functional TF-TF network and conserved motif-centered TF-DNA networks to construct a core TF network defined by mutual cross-regulation among core TFs. We found that core TF ARG (Abscisic acid response element binding factor-like Root Growth regulator) represses BRG (Brassinosteroid enhanced expression-like Root Growth regulator) expression through binding to its promoter at a conserved binding site. ARG and BRG antagonistically regulate Phytochrome-interacting factor-like Root Growth regulator (PRG) and combinatorially regulate some other core TFs. These core TFs form complex regulatory circuits to integrate light and multiple hormone signaling pathways and maintain root growth in response to varying degrees of water stress. Our study provides valuable information to unravel the complicated mechanisms of molecular networks involved in the regulation of root growth under water deficit.

plant biology↗