Biology subjects

Xiong, J.

Publications and source records attributed to Xiong, J..

At least 73 records · Page 4Linked to original sources

bioRxiv2022

Programming the lifestyles of engineered bacteria for cancer therapy

Bacteria can be genetically engineered to act as therapeutic delivery vehicles in the treatment of tumors, killing cancer cells or activating the immune system. This is known as Bacteria-Mediated Cancer Therapy (BMCT). Tumor invasion, colonization and tumor regression are major biological events, which are directly associated with antitumor effects and are uncontrollable due to the influence of tumor microenvironments during the BMCT process. Here, we developed a genetic circuit for dynamically programming bacterial lifestyles (planktonic, biofilm or lysis), to precisely manipulate the process of bacterial adhesion, colonization and drug release in BMCT process, via hierarchical modulation of the lighting power density (LPD) of near-infrared (NIR) light. The deep tissue penetration of NIR offers us a modality for spatiotemporal and noninvasive control of bacterial genetic circuits in vivo. By combining computational modeling with high throughput characterization device, we optimized the genetic circuits in engineered bacteria to program the process of bacterial lifestyle transitions by altering the illumination scheme of NIR. Our results showed that programming intratumoral bacterial lifestyle transitions allows precise control of multiple key steps throughout the BMCT process, and therapeutic efficacy can be greatly improved by controlling the localization and dosage of therapeutic agents via optimizing the illumination scheme.

synthetic biology↗

bioRxiv2022

DNA binding domain undergoes dynamic and selective protein-protein interactions to facilitate CTCF insulation

CTCF is required for three-dimensional chromatin organization and a predominant insulator protein. However, its roles in insulating enhancers have not been fully explained in 3D nuclear organization. Here, we found that the CTCF DNA binding domain (DBD) forms dynamic self-interacting clusters. We next investigated the spatial relationships between these clusters and other transcription regulators with a light-induced imaging system. Strikingly, CTCF DBD clusters were found to incorporate other insulator proteins but are not coenriched with transcriptional activators in the nucleus. This property is not observed in other domains of CTCF or the DBDs of other transcription factors. Moreover, endogenous CTCF shows a phenotype consistent with the DBD by forming small protein clusters and interacts less transcriptional activators bound, CTCF motif arrays. Our results reveal an interesting phenomenon that CTCF DBD interacts with insulator proteins and selectively localizes to nuclear positions with lower concentrations of transcriptional activators, providing new insights into the insulation function of CTCF.

molecular biology↗

bioRxiv2022

Differential integration of activation and repression signals in a multi-enhancer system

Transcription in the early Drosophila blastoderm is coordinated by the collective action of hundreds of enhancers. Many genes are controlled by so-called "shadow enhancers," which provide resilience to environment or genetic insult, allowing the embryo to robustly generate a precise transcriptional pattern. Emerging evidence suggests that many shadow enhancer pairs do not drive identical expression patterns, however the biological significance of this remains unclear. In this study we characterize the shadow enhancer pair controlling the gene short gastrulation (sog). We removed either the intronic proximal enhancer or the upstream distal enhancer, and monitored sog transcriptional kinetics. Notably, each enhancer differs in sog spatial expression, timing of activation, and RNA Polymerase II loading rates. Additionally, modeling of individual enhancer activities demonstrates that these enhancers integrate activation and repression signals differently. While activation is due to the sum of the two enhancer activities, repression appears to depend on synergistic effects between enhancers. Finally, we examined the downstream signaling consequences resulting from the loss of either enhancer, and found changes in tissue patterning that are well explained by the differences in transcriptional kinetics measured. SUMMARY STATEMENTNon-intuitive shadow enhancer synergies are revealed by measuring transcriptional kinetics at the endogenous short gastrulation locus, giving rise to distinct patterning consequences in the dorsal ectoderm of Drosophila embryos.

developmental biology↗

bioRxiv2021

Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells

Human pluripotent stem cell (hPSC)-induced NK (iNK) cells are a promising "off-the-shelf" cell product for universal immune therapy. Conventional methods for iNK cell regeneration from hPSCs include embryonic body-formation and feeder-based expansion steps, which bring instability, time-consuming, and high costs for manufacture. In this study, we develop an embryonic body-free, organoid aggregate method for NK cell regeneration from hPSCs. In a short time window of 27-day induction, millions of hPSC input can produce over billions of iNK cells without the necessity of NK cell-expansion feeders. The iNK cells highly express classical toxic granule proteins, apoptosis-inducing ligands, as well as abundant activating and inhibitory receptors. Functionally, the iNK cells eradicate human tumor cells by mechanisms of direct cytotoxity, apoptosis, and antibody-dependent cellular cytotoxicity. This study provides a reliable scale-up method for regenerating human NK cells from hPSCs, which promotes the universal availability of NK cell products for immune therapy.

immunology↗

bioRxiv2021

Hoxb5 reprograms murine multipotent blood progenitors into hematopoietic stem cell-like cells

The expression of transcription factor Hoxb5 specifically marks the functional hematopoietic stem cells (HSC) in mice. However, our recent work demonstrated that ectopic expression of Hoxb5 exerted little effect on HSC but could convert B cell progenitors into functional T cells in vivo. Thus, cell type- and development stage-specific roles of Hoxb5 in hematopoietic hierarchy await more extensive exploration. Here, with a mouse strain engineered with conditional expression of Hoxb5, we unveiled that induced expression of Hoxb5 in mouse multipotent progenitor cells (MPP) led to the generation of a de novo Sca1+cKit+Mac1+CD48+ (Mac1+CD48+SK) cell type, which has the ability to repopulate long-term multi-lineage hematopoiesis in serial transplant recipients. RNA-seq analyses showed that Mac1+CD48+SK cells exhibited an acquired machinery of DNA replication and cell division, which resembled nature fetal liver HSC cells (FL HSC). In short, our current study uncovers that Hoxb5 is able to empower MPP with self-renewal potential, thereby providing new strategies to reprogram blood progenitor cells into HSC-like cells.

cell biology↗

bioRxiv2021

Regeneration of humoral immunity from pluripotent stem cells by defined transcription factors

Regeneration of humoral immunity from pluripotent stem cells (PSCs) is a crucial aim in translational medicine. However, reconstitution of complete, sustained, and functional B lymphopoiesis from PSCs has not yet been developed. Here, we successfully achieved regenerative B lymphopoiesis in B-cell deficient animals transplanted with PSC-derived hematopoietic progenitors (iHPCs) guided by synergistic expression of Runx1, Hoxa9, and Lhx2. Upon transplantation, the iHPCs immediately gave rise to pro/pre-B cells in recipients bone marrow, which were able to further differentiate into the entire B cell lineages, including innate B-1a, B-1b, MZ B cells, as well as adaptive FO B cells. In responding to antigen stimuli, the regenerative B cells produced adaptive humoral immune responses, sustained a prolonged antigen-specific antibody production, and formed immune-memory. Particularly, the regenerative B cells in spleen showed developing patterns of immunoglobulin chain-switch and hyper-mutation via a cross-talk with the host T follicular helper cells, which eventually formed T cell-dependent humoral responses. This study provides de novo evidence that B lymphopoiesis can be regenerated from PSCs via a HSC-independent approach, which provides insights into treating B-cell related humoral deficiencies using PSCs as unlimited cell resource.

immunology↗

bioRxiv2021

A novel MRI-based data fusion methodology for efficient, personalised, compliant simulations of aortic haemodynamics

We present a novel, cost-efficient methodology to simulate aortic haemo-dynamics in a patient-specific, compliant aorta using an MRI data fusion process. Based on a previously-developed Moving Boundary Method, this technique circumvents the high computational cost and numerous structural modelling assumptions required by traditional Fluid-Structure Interaction techniques. Without the need for Computed Tomography (CT) data, the MRI images required to construct the simulation can be obtained during a single imaging session. Black Blood MR Angiography and 2D Cine-MRI data were used to reconstruct the luminal geometry and calibrate wall movement specifically to each region of the aorta. 4D-Flow MRI and non-invasive pressure measurements informed patient-specific inlet and outlet boundary conditions. Luminal area closely matched 2D Cine-MRI measurements with a mean error of less than 4.6% across the cardiac cycle, while physiological pressure and flow distributions were simulated to within 3.3% of patient-specific targets. Moderate agreement with 4D-Flow MRI velocity data was observed. Despite lower peak velocity, an equivalent rigid-wall simulation predicted a mean Time-Averaged Wall Shear Stress (TAWSS) 13% higher than the compliant simulation. The agreement observed between compliant simulation results and MRI data is testament to the accuracy and efficiency of this MRI-based simulation technique.

bioengineering↗

bioRxiv2021

Class II LBD genes ZmLBD5 and ZmLBD33 regulate gibberellin and abscisic acid biosynthesis

Lateral organ boundaries domain (LBD) proteins are plant-specific transcription factors. Class I LBD members are widely reported to be pivotal for organ development, however, the role of class II members is unknown in cereal crops. Class II LBD proteins are distinguished from class I by the lack of a Gly-Ala-Ser (GAS) peptide and leucine-zipper-like coiled-coil domain, which is thought to be essential for protein dimerization. In this study, ZmLBD5 and ZmLBD33 form homo- and hetero-dimers, like class I members. At seedling stage, ZmLBD5 promoted biomass accumulation (shoot dry weight and root dry weight), root development (root length, root number, and root volume), and organ expansion (leaf area), while ZmLBD33 repressed these processes and display a dwarf phenotype. Both ZmLBD5 and ZmLBD33 displayed negative roles in drought tolerance mainly by increasing stomatal density and stomatal aperture. RNA sequencing, gene ontology enrichment analysis, and transient luciferase expression assays indicated that ZmLBD5 and ZmLBD33 are mainly involved in the regulation of the TPS-KS-GA2ox gene module, which comprises key enzymatic genes upstream of GA and ABA biosynthesis. GA1 content increased in ZmLBD5-overexpressing seedlings, while GA3 and abscisic acid content decreased in both transgenic seedlings. Consequently, exogenous GA1 or GA3 undoubtedly rescued the dwarf phenotype of ZmLBD33-overexpressing plants, with GA1 performing better. The study of ZmLBD5 and ZmLBD33 sheds light on the function of the class II LBD gene family in maize.

plant biology↗

bioRxiv2020

Trans-Golgi network-lipid droplet contacts maintain the TGN integrity and function via lipid transfer activities of VPS13B

While the physical interactions between the Golgi apparatus (Golgi) and lipid droplets (LDs) have been suggested through system-level imaging, the bona fide and functional Golgi-LD membrane contact sites (MCSs) remain largely uncharacterized. Here, we demonstrate that vacuolar protein sorting-associated protein 13B (VPS13B) mediates trans-Golgi network (TGN)-LD interactions. VPS13B is specifically accumulated at TGN-LD MCSs with its C-terminal region targeting LDs via an amphipathic helix while a putative WD40 module and a C-terminal Pleckstrin homology (PH) domain independently recognizing TGN via directly binding to Rab6. A putative lipid transfer domain (LTD) at the N-terminal portion of VPS13B binds glycerophospholipids in vitro. VPS13B suppression results in severe fragmentation of the TGN, an effect that can be almost completely rescued by the expression of VPS13B-LTD. Collectively, our findings demonstrate that VPS13B mediates lipid transfer at TGN-LD MCSs to maintain TGN integrity and function.

cell biology↗

bioRxiv2020

Human Embryonic Stem Cell-derived Lung Organoids: a Model for SARS-CoV-2 Infection and Drug Test

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we demonstrated that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids. Ciliated cells, alveolar type 2 (AT2) cells and rare club cells were virus target cells. Electron microscopy captured typical replication, assembly and release ultrastructures and revealed the presence of viruses within lamellar bodies in AT2 cells. Virus infection induced more severe cell death in alveolar organoids than in airway organoids. Additionally, RNA-seq revealed early cell response to SARS-CoV-2 infection and an unexpected downregulation of ACE2 mRNA. Further, compared to the transmembrane protease, serine 2 (TMPRSS2) inhibitor camostat, the nucleotide analog prodrug Remdesivir potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model for SARS-CoV-2 infection and drug discovery.

microbiology↗

bioRxiv2020

A Pan-Cancer Blueprint of the Heterogeneous Tumour Microenvironment Revealed by Single-Cell Profiling

AO_SCPLOWBSTRACTC_SCPLOWThe stromal compartment of the tumour microenvironment consists of a heterogeneous set of tissue-resident and tumour-infiltrating cells, which are profoundly moulded by cancer cells. An outstanding question is to what extent this heterogeneity is similar between cancers affecting different organs. Here, we profile 233,591 single cells from patients with lung, colorectal, ovary and breast cancer (n=36) and construct a pan-cancer blueprint of stromal cell heterogeneity using different single-cell RNA and protein-based technologies. We identify 68 stromal cell populations, of which 46 are shared between cancer types and 22 are unique. We also characterise each population phenotypically by highlighting its marker genes, transcription factors, metabolic activities and tissue-specific expression differences. Resident cell types are characterised by substantial tissue specificity, while tumour-infiltrating cell types are largely shared across cancer types. Finally, by applying the blueprint to melanoma tumours treated with checkpoint immunotherapy and identifying a naive CD4+ T-cell phenotype predictive of response to checkpoint immunotherapy, we illustrate how it can serve as a guide to interpret scRNA-seq data. In conclusion, by providing a comprehensive blueprint through an interactive web server, we generate a first panoramic view on the shared complexity of stromal cells in different cancers.

cancer biology↗

bioRxiv2020

Purine metabolism regulates DNA repair and therapy resistance in glioblastoma

Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance, and new strategies that are effective independent of genotype are urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of GBM, we found that purine metabolites strongly correlated with radiation resistance. Inhibiting purine, but not pyrimidine, synthesis radiosensitized GBM cells and patient-derived neurospheres by impairing DNA repair in a nucleoside-dependent fashion. Likewise, administration of exogenous purine nucleosides protected sensitive GBM models from radiation by promoting DNA repair. Combining an FDA-approved inhibitor of de novo purine synthesis with radiation arrested growth in GBM xenograft models and depleted intratumoral guanylates. High expression of the rate-limiting enzyme of de novo GTP synthesis was associated with shorter survival in GBM patients. Together, these findings indicate that inhibiting de novo purine synthesis may be a promising strategy to overcome therapy resistance in this genomically heterogeneous disease.

neuroscience↗

bioRxiv2020

DNA Methylation Repels Binding of HIF Transcription Factors to Maintain Tumour Immunotolerance

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSHypoxia is pervasive in cancer and other diseases. Cells sense and adapt to hypoxia by activating hypoxia-inducible transcription factors (HIFs), but it is still an outstanding question why cell types differ in their transcriptional response to hypoxia. ResultsHere, we report that HIFs fail to bind CpG dinucleotides that are methylated in their consensus binding sequence, both in in vitro biochemical binding assays and in vivo studies of differentially methylated isogenic cell lines. Based on in silico structural modelling, we show that 5-methylcytosine indeed causes steric hindrance in the HIF binding pocket. A model wherein cell-type-specific methylation landscapes, as laid-down by the differential expression and binding of other transcription factors under normoxia control cell-type-specific hypoxia responses is observed. We also discover ectopic HIF binding sites in repeat regions which are normally methylated. Genetic and pharmacological DNA demethylation, but also cancer-associated DNA hypomethylation, expose these binding sites, inducing HIF-dependent expression of cryptic transcripts. In line with such cryptic transcripts being more prone to cause double-stranded RNA and viral mimicry, we observe low DNA methylation and high cryptic transcript expression in tumours with high immune checkpoint expression, but not in tumours with low immune checkpoint expression, where they would compromise tumour immunotolerance. In a low-immunogenic tumour model, DNA demethylation upregulates cryptic transcript expression in a HIF-dependent manner, causing immune activation and reducing tumour growth. ConclusionsOur data elucidate the mechanism underlying cell-type specific responses to hypoxia, and suggest DNA methylation and hypoxia to underlie tumour immunotolerance.

genomics↗

bioRxiv2020

Colorectal cancer marker identification using the aging immune system-related blood cell DNA methylome

ObjectiveThere is a body of evidence that the aging immune system is linked to cancer. Here, we hypothesized that ubiquitination might play a key gatekeeper role in immune system aging and tumorigenesis in CRC. Therefore, we will systematically study the DNA methylation of ubiquitination genes and screen candidate CRC marker that are correlated with both aging and immune cell compositions. DesignThrough aging- and immune-related DNA methylation data, we investigated the DNA methylation regulation changes in promoters with other regions of genes during aging and their association with the immune cell proportion in the circulating whole blood of healthy individuals. Then, by collecting a cohort of 100 colon cancer patients and 50 healthy individuals, we used nucleic acid mass spectrometry to test whether ubiquitination genes can be used as candidate markers for the early screening of CRC. ResultsThe biological analyses for aging- and CD4 T cell proportion-derived differential genes showed that they are associated with ubiquitination. Among them, DZIP3 was significantly associated with both aging (P-value = 3.86E-06) and CD4 T cell proportion (P-value = 1.97E-05) in circulating blood. Then, we validated that the 1st exon DNA methylation of DZIP3 could predict the onset of early stage CRC (AUC = 0.833, OR = 8.82) and all pTNM stages of CRC (AUC = 0.782, OR = 5.70). ConclusionsThe epigenetically regulated ubiquitination plays an important role in immune aging and tumorigenesis. DNA methylation characteristic of DZIP3 can be used as a promising marker of CRC early screening. Summary boxO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIThe aging immune system is associated with cancer. C_LIO_LIUbiquitination plays potent roles in regulating a variety of signals in both innate and adaptive immune cells. C_LIO_LIThe abnormalities of ubiquitination are closely related to the occurrence of various tumors. C_LIO_LIBlood cell DNA methylome analysis provides a promising tool to probe the key components of immune cell dysregulation in aging and tumorigenesis. C_LI What are the new findings?O_LIThe aging- and immune cell proportion-derived differential genes are associated with ubiquitination. C_LIO_LIThe epigenetically regulated ubiquitination plays an important role in immune aging and tumorigenesis. C_LIO_LIDNA methylation characteristic of DZIP3, an E3 ubiquitin ligase with no reports on its function in immune cells and tumorigenesis, can be used as a promising markers of CRC early screening. C_LI How might it impact on clinical practice in the foreseeable future?O_LIThe in-depth study for DNA methylome of ubiquitination will open up a new path for the study of CRC pathogenesis, diagnosis and treatment. C_LIO_LIIn addition, DZIP3-focused screening technique only needs to extract the whole blood of individuals for MassARRAY analysis; the samples are easy to obtain, and the results are objective. Therefore, this method may have important applications in clinical CRC screening. C_LI

cancer biology↗

bioRxiv2020

A strategy for complete telomere-to-telomere assembly of ciliate macronuclear genome using ultra-high coverage Nanopore data

Ciliates contain two kinds of nuclei: the germline micronucleus (MIC) and the somatic macronucleus (MAC) in a single cell. The MAC usually have fragmented chromosomes. These fragmented chromosomes, capped with telomeres at both ends, could be gene size to several megabases in length among different ciliate species. So far, no telomere-to-telomere assembly of entire MAC genome in ciliate species is finished. Development of the third generation sequencing technologies allows to generate sequencing reads up to megabases in length that could possibly span an entire MAC chromosome. Taking advantage of ultra-long Nanopore reads, we established a simple strategy for the complete assembly of ciliate MAC genomes. Using this strategy, we assembled the complete MAC genomes of two ciliate species Tetrahymena thermophila and Tetrahymena shanghaiensis, composed of 181 and 214 chromosomes telomere-to-telomere respectively. The established strategy as well as the high-quality genome data will provide a useful approach for ciliate genome assembly, and a valuable community resource for further biological, evolutionary and population genomic studies.

genomics↗

bioRxiv2020

Mining the Selective Remodeling of DNA Methylation in Promoter Regions to Identify Robust Gene-Level Associations with Phenotype

Epigenetics is an essential biological frontier linking genetics to the environment, where DNA methylation is one of the most studied epigenetic events. In recent years, through the epigenome-wide association study (EWAS), researchers have identified thousands of phenotype-related methylation sites. However, the overlap between identified phenotype-related DNA methylation sites are often quite small, and it might clue to methylation remodeling has a certain degree of randomness within the genome. Thus, the identification of robust gene-phenotype associations is crucial for interpreting pathogenesis. How to integrate the methylation values of different sites on the same gene and to mining the DNA methylation at the gene level remains a challenge. A recent study found that the DNA methylation difference of the gene body and promoter region has a strong correlation with gene expression. In this study, we proposed a Statistical difference of DNA Methylation between Promoter and Other Body Region (SIMPO) algorithm to extract DNA methylation values at the gene level. First, by choosing to smoke as an environmental exposure factor, our method led to significant improvements in gene overlaps (from 5% to 17%) between different datasets. In addition, the biological significance of these genes ([~]23%) are significantly better than those identified by traditional probe-based methods ([~]18%, P-value = 5.18e-03). Then, we selected two disease content (e.g., insulin resistance and Parkinsons disease) to show that the biological efficiency of disease-related gene identification increased from 15.43% to 44.44% (P-value = 1.20e-28). Thus, our results declare that mining the selective remodeling of DNA methylation in promoter regions can identify robust gene-level associations with phenotype, and the characteristic remodeling of a given genes promoter region can reflect the essence of disease.

bioinformatics↗

bioRxiv2019

Extensive Mammalian Germline Genome Engineering

Xenotransplantation, specifically the use of porcine organs for human transplantation, has long been sought after as an alternative for patients suffering from organ failure. However, clinical application of this approach has been impeded by two main hurdles: 1) risk of transmission of porcine endogenous retroviruses (PERVs) and 2) molecular incompatibilities between donor pigs and humans which culminate in rejection of the graft. We previously demonstrated that all 25 copies of the PERV elements in the pig genome could be inactivated and live pigs successfully generated. In this study, we improved the scale of porcine germline editing from targeting a single repetitive locus with CRISPR to engineering 13 different genes using multiple genome engineering methods. we engineered the pig genome at 42 alleles using CRISPR-Cas9 and transposon and produced PERVKO{middle dot}3KO{middle dot}9TG pigs which carry PERV inactivation, xeno-antigen KO and 9 effective human transgenes. The engineered pigs exhibit normal physiology, fertility, and germline transmission of the edited alleles. In vitro assays demonstrated that these pigs gain significant resistance to human humoral and cell mediated damage, and coagulation dysregulations, similar to that of allotransplantation. Successful creation of PERVKO{middle dot}3KO{middle dot}9TG pigs represents a significant step forward towards safe and effective porcine xenotransplantation, which also represents a synthetic biology accomplishment of engineering novel functions in a living organism. One Sentence SummaryExtensive genome engineering is applied to modify pigs for safe and immune compatible organs for human transplantation

synthetic biology↗

bioRxiv2019

Lateral mechanical impedance rather than frontal, promotes cortical expansion of roots

It has long been considered that mechanical impedance on root will restrict root elongation and consequently promote radial growth. However, we did observe radial expansion but not elongation restriction in maize seedlings after short growth in sands. Mechanical impedance of soil can be classified into frontal- and lateral-type based on the interaction site of root. Therefore, we suspected that radial expansion might be mainly stimulated by lateral rather than frontal impedance. To verify our speculation, frontal and lateral impedance was provided separately. Small plastic caps were used to provide unique frontal impedance on root tip and cylindrical plastic containers were used to provide lateral impedance. Plastic caps could reduce root length remarkably. However, the radial expansion of plastic-cap-fitted roots was significantly inferior to that of the sand-cultured roots. Microstructural analysis revealed that sand-condition thickened root largely dependents on cortical expansion, whereas plastic cap did it mainly by thickening stele. In cylindrical plastic containers, mechanical impedance came only from the lateral direction and promoted the expansion of cortex just as sand-condition. Thus, we proposed that the expansion of the cortex and the consequent radial growth is mainly due to lateral impedance when growing in sands.

plant biology↗