Biology subjects

Mao, L.

Publications and source records attributed to Mao, L..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Spatial transcriptomics of developing wheat seed reveals radial expression patterns in endosperm and subgenome biased expression of key genes

Gene expression of developing seeds drives essential processes such as nutrient storage, stress tolerance and germination. However, the spatial organisation of gene expression within the complex structure of the seed remains largely unexplored. Here we report the use of the STOmics spatial transcriptomics platform to visualise spatial expression patterns in the wheat (Triticum aestivum) seed at the critical period of grain filling in mid seed development. We analysed >4,000,000 spatially resolved transcripts, achieving subcellular resolution of transcript localization across multiple tissue domains, and identified gene expression clusters linked to eight functional cellular groups. Notably, our analysis characterised four distinct clusters within the endosperm, which exhibited radial expression patterns from the inner to outer regions of the grain, and identified novel marker gene candidates for the clusters found. We further investigated known tissue-specific genes and identified subgenome biased expression between paralogs of puroindoline-B, metallothionein protein, and -amylase/subtilisin inhibitor. These findings provide new detail about gene expression across and within different functional cellular groups of the developing seed and demonstrate that spatial transcriptomics could further our understanding of subgenome differences in polyploid plants.

plant biology↗

bioRxiv2025

Shared molecular regulation of quiescence in neural and glioma stem cells reveals therapeutic vulnerabilities.

Quiescence, a reversible state of cell-cycle arrest, is an adaptive feature of many adult tissue stem cells, including those in the adult brain. In gliomas, brain tumour stem cells that reside in a quiescent state preferentially survive chemotherapy and radiotherapy, highlighting their critical role in therapy resistance and disease progression. To date, it remains unclear whether the molecular programs governing these states are functionally conserved between neural stem cells and brain tumour stem cells. Here, we establish novel in vitro models to study quiescence and find that glioma stem cells are markedly more resistant to entering quiescence than neural stem cells, suggesting that glioma stem cell quiescence more closely resembles a slow-cycling phenotype or shallow quiescence. Nonetheless, direct comparison of quiescent neural stem cells and quiescent/slow-cycling glioma stem cells, as they transition towards proliferation, reveals conserved gene expression trajectories, indicating shared molecular mechanisms. Furthermore, we find that pathways influencing quiescence in neural stem cells exert similar effects in glioma stem cells, underscoring the functional parallels between these populations. Finally, we identify that inhibition of TGF-{beta} signalling might provide an avenue to improve current standard-of-care treatments by targeting quiescent glioma stem cells. Note on version 2This version corrects two figure errors and expands the Methods. The conclusions of are unchanged. ImagesIn version 1, debris adjacent to the organoid had been digitally removed from the drug-treated image in Figure 6D. The unmodified original is restored here. Images within Figures 3A and 6D have each been processed identically to one another. Scattered cellular debris was present to a similar extent in control and drug-treated samples. O_FIG O_LINKSMALLFIG WIDTH=153 HEIGHT=200 SRC="FIGDIR/small/634421v2_fig6.gif" ALT="Figure 6"> View larger version (51K): org.highwire.dtl.DTLVardef@19aef83org.highwire.dtl.DTLVardef@e2c1e1org.highwire.dtl.DTLVardef@126bf22org.highwire.dtl.DTLVardef@ce7acd_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 6:C_FLOATNO TGF--R1 inhibition drives GSCs out of a quiescent state. (A) QBC395 cells were cultured in BMP4 quiescence media plus inhibitors for three days. Graphs show percentage of proliferating GSCs (SOX2+Ki67+) over total GSCs (SOX2+). Data were normalised to mean of quiescence media alone. (B) QBC395 cells were cultured in palbociclib quiescence media plus inhibitors for three days. Graphs show proportion of proliferating GSCs (SOX2+Ki67+) over total GSCs (SOX2+). Data were first normalised to vehicle control for each independent experiment and then quiescence media alone. (C) Schematic of glioblastoma organoid generation. Experiments began within 1-2 weeks of derivation to maximise cellular heterogeneity. Protocol adapted from Jacob and colleagues (60). (D) Image of glioblastoma organoid treated with 30 {micro}M LY-364397 or DMSO vehicle (control) for three days, stained for SOX2 (cyan) and Ki67 (magenta). Dashed lines demarcate organoid boundary. Scale bar: 100 {micro}m. Scattered cellular debris was observed in both control and drug-treated samples to a similar extent. (E) Proportion of proliferating GSCs (SOX2+Ki67+) over total GSCs (SOX2+) after glioblastoma organoids were cultured in the presence of inhibitors. Data were normalised to mean of respective vehicle control. Graphs in (A, B, E) show mean {+/-} SEM. Experiments in (A, B) represent independent experiments on separate passages (n=3-4). Dots in (E) represent individual organoids. Statistics: one-way repeated measures ANOVA with Holm-Sidaks multiple comparisons test in (A, B). Two-way ANOVA in (E) with multiple comparisons t-test. *P < 0.05, **P < 0.01, ***P < 0.001. Panel C created with BioRender (Agreement number: FY289ELRZ5). C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=52 SRC="FIGDIR/small/634421v2_fig3.gif" ALT="Figure 3"> View larger version (21K): org.highwire.dtl.DTLVardef@1e04d0corg.highwire.dtl.DTLVardef@e25e26org.highwire.dtl.DTLVardef@1934ab0org.highwire.dtl.DTLVardef@10c77fb_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 3:C_FLOATNO BMP4 and palbociclib treatment induces patient-derived GSCs into shallow versus deep states of quiescence, respectively. (A) Treatment with 16 ng/mL BMP4 markedly reduces the proportion of proliferating NSCs (SOX2+Ki67+) in primary adult mouse SVZ cultures. (B) Treatment with 16 ng/mL BMP4 modestly reduces the proportion of proliferating GSCs (SOX2+Ki67+) in primary patient-derived cultures (QBC395 cell line). (C) Concentration-response curve of mouse NSCs and patient-derived GSCs (QBC395 cell line) treated with BMP4, measuring proportion of proliferating stem cells (SOX2+Ki67+) relative to control media. Data were normalised to mean of control. (D) Palbociclib treatment markedly reduces the proportion of proliferating GSCs (SOX2+Ki67+) relative to control media. Data were normalised to mean of control. GSC graphs in (C, D) show mean {+/-} SEM of independent experiments conducted on separate passages (n=3-4). NSC graph in (C) shows mean {+/-} SEM of individual cell lines derived from SVZ of different mice (n=4). Scale bar: 15 {micro}m in (A, B). Cross in (D) represents concentration-response at 200 nM. Statistics in (C): two-way ANOVA reporting main effect of cell-line. C_FIG DataThe glioblastoma organoid data in Figure 6E have been updated following re-imaging and blinded re-analysis. Reported effect sizes have changed slightly; the conclusions are unchanged. Figure S2 has likewise been updated following re-imaging and re-analysis. MethodsThe Methods have been expanded to describe the analysis more fully, including data exclusion criteria, normalisation, and blinding. Minor changes to figure legends and the main text are not itemised.

cancer biology↗

bioRxiv2024

Effects of Forefoot versus Rearfoot Landing on Biomechanical Risk Factors for Lower Limb Injuries and Performance During Stop-Jump Tasks

BackgroundLower limb injuries commonly occur during sudden deceleration movements. Instructing landing with forefoot or rearfoot is hard to answer, especially considering the injury prevention and keep the performance. Therefore, the purpose of this study is to evaluate the effect of the forefoot and rearfoot landing on the biomechanical risk of lower limb injury prevention and performance during the stop-jumping task. MethodTwenty-three male health subjects were recruited for this study. During a stop-jumping task, three-dimensional kinematic and kinetic, and performance data were collected under two conditions: forefoot landing at initial ground contact and rearfoot landing at initial ground contact. Statistical parametric mapping analysis was used to compare the differences between different landing strategies. ResultSignificant differences were found in ankle internal rotation angle and ankle joint moment at foot initial contact with ground between different landing strategies. Landing with forefoot has shorter stance time compared with landing with rearfoot. In the rearfoot strike, posterior ground reaction force (GRF) and GRF inclination angle were smaller than forefoot strike in 0-14% of the stance phase. ConclusionLanding with forefoot may decrease the risk of non-contact anterior cruciate ligament injuries and have an advancement in quick reaction time, as indicated by decreased stance time, but the risk of lateral ankle sprain may increase for the stop-jump task.

bioengineering↗

bioRxiv2024

Key Regulatory Elements of the TGFbeta-LRRC15 Axis Predict Disease Progression and Immunotherapy Resistance Across Cancer Types

Transforming growth factor-beta (TGF{beta}) has dual roles in cancer, initially suppressing tumors but later promoting metastasis and immune evasion. Efforts to inhibit TGF{beta} have been largely unsuccessful due to significant toxicity and indiscriminate immunosuppression. Leucine-rich repeat-containing protein 15 (LRRC15) is a TGF{beta}-regulated antigen expressed by mesenchymal-derived cancer cells and cancer-associated fibroblasts (CAFs). In preclinical studies, ablation of TGF{beta}-driven LRRC15+ CAFs increased tumor infiltration of CD8+ T cells. However, the underlying pathobiological mechanisms prompting TGF{beta}s upregulation of LRRC15 expression are unclear. Using an integrated approach combining functional compound screening with single-cell RNA sequencing, we reveal key genomic features regulating TGF{beta}s ability to increase LRRC15 expression on cancer cells. Construction of gene regulatory networks converged our analyses on four key genes--MMP2, SPARC, TGF{beta}R2, and WNT5B--central to TGF{beta}-induced LRRC15 pathobiology. Validation of these genes in cell models and their use in predicting immunotherapy responses highlight their potential in refining immunotherapy strategies and personalizing co-treatment options.

pharmacology and toxicology↗

bioRxiv2024

NAD+ - and EVA1-C-dependent reversal of neurological deficits is mediated by differential alternative RNA splicing in tauopathic animal models

Aberrant alternative splicing (ASEs) is an aging hallmark to Alzheimers Disease (AD). Although NAD+ and related metabolites can slow down AD, NAD+ on ASEs in AD remain unclear. Mouse transcriptomic data revealed NR-induced ASEs, focusing on the Eva1-C locus. AI-based algorithms predicted EVA1-C protein structures and protein-protein interactions. AD postmortem brain samples and tauopathy models including transgenic mice and worm was used for validation. NAD+ abundance/metabolic status modulates ASEs and the expression of EVA1-C isoforms, which in turn regulate the interaction with BAG-1 and HSP70 proteins. Importantly, EVA1-C is dramatically reduced in 20 Braak 5/6 AD patients compared to cognitive normal humans in different brain regions. NAD+ metabolism modulates abundance of specific mRNA isoforms, and that ASEs influence disease progression in model tauopathies and potentially AD. These results could facilitate future development of NAD+-based splice-switching therapeutics for AD. TeaserUnveiling the Link Between NAD+ Metabolism and Alzheimers Disease: Discovering the Role of Alternative RNA Splicing in Disease Progression and Potential Therapeutic Targets

neuroscience↗

bioRxiv2024

Unraveling transposable element-mediated regulatory landscape in diverse human immune cells

Transposable elements (TEs) are key contributors to genetic novelty. Despite increasing evidence of their importance, their roles in shaping the regulatory landscape of diverse immune cell populations remain largely unclear. Using single-cell multiome data from human peripheral blood mononuclear cells, we annotated the cell-specific cis-regulatory elements for major immune cell populations and identified a highly cell-specific signature of the overrepresented TE families. Focusing on monocytes that bear fast-evolving transcriptomes, we found that high proportions of their enhancers are TE-derived and bound by multiple pioneer transcription factors. Among them, we confirmed that the core myeloid regulator SPI1 can bind and regulate hundreds of TE-derived enhancers, which further affect the expression of adjacent immune genes. Additionally, interspecies comparison reveals that non-conserved monocyte enhancers are frequently generated by lineage-specific TE insertions, and correlate with the evolved gene expression between human and mouse. Overall, our study supports the importance of TEs in shaping the regulatory landscape of diverse immune cell populations.

genomics↗

bioRxiv2024

Multiplexed spatial mapping of chromatin features, transcriptome, and proteins in tissues

The phenotypic and functional states of a cell are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome, and metabolome. Spatial omics approaches have enabled the capture of information from different molecular layers directly in the tissue context. However, current technologies are limited to map one to two modalities at the same time, providing an incomplete representation of cellular identity. Such data is inadequate to fully understand complex biological systems and their underlying regulatory mechanisms. Here we present spatial-Mux-seq, a multi-modal spatial technology that allows simultaneous profiling of five different modalities, including genome-wide profiles of two histone modifications and open chromatin, whole transcriptome, and a panel of proteins at tissue scale and cellular level in a spatially resolved manner. We applied this technology to generate multi-modal tissue maps in mouse embryos and mouse brains, which discriminated more cell types and states than unimodal data. We investigated the spatiotemporal relationship between histone modifications, chromatin accessibility, gene and protein expression in neuron differentiation revealing the relationship between tissue organization, function, and gene regulatory networks. We were able to identify a radial glia spatial niche and revealed spatially changing gradient of epigenetic signals in this region. Moreover, we revealed previously unappreciated involvement of repressive histone marks in the mouse hippocampus. Collectively, the spatial multi-omics approach heralds a new era for characterizing tissue and cellular heterogeneity that single modality studies alone could not reveal.

genetics↗

bioRxiv2024

The FBA Solution Space Kernel -- Introduction and Illustrative Examples

BackgroundThe solution space of an FBA-based model of cellular metabolism, can be characterised by extraction of a bounded, low dimensional kernel (the SSK) that facilitates perceiving it as a geometric object in multidimensional flux space. The aim is to produce an amenable description, intermediate between the single feasible extreme flux of FBA, and the intractable proliferation of extreme modes in conventional solution space descriptions. Fluxes that remain fixed are separated off while the focus of interest is put on the subset of variable fluxes that have a nonzero but finite range of values. For un-bounded fluxes, a finite subrange that geometrically corresponds to the variable flux range is determined and is supplemented by a limited set of rays that encapsulates their unbounded aspects. In this way the kernel emphasises the realistic range of flux variation allowed in the interconnected biochemical network by e.g. limited nutrient uptake, an optimised objective and other model constraints. This work builds on the full presentation of the SSK approach in a research monograph. MethodsCalculations are performed with the publicly available software package SSKernel, the source code and user manual of which is included as a supplementary file. ResultsIt is demonstrated how knowledge of the SSK and accompanying rays can be exploited to explore representative flux states of the metabolic network. Noting that bioengineering interventions such as gene knockouts modify the solution space, new tools based on the SSK analysis are presented here that predict the effects of such interventions on a target flux constructed to represent a desired metabolic output. A simple metabolic model is used first to demonstrate the special concepts and constructions needed to define and compute the SSK. The demonstration model is tweaked to produce typical behaviours of larger models, but with kernels in 1,2 or 3 dimensions that are explicitly displayed to visualise the concepts. General applicability to models where visualisation is inaccessible, is illustrated by showing evaluation of potential bioengineering strategies for a genome scale model. ConclusionsSSKernel is a flexible interactive tool that facilitates an overview of the FBA solution space as a multidimensional geometric object, in terms of a manageable number of parameters. It allows exploration of effects on this solution space from metabolic interventions, and can be used to investigate bioengineering strategies to manipulate cellular metabolism.

systems biology↗

bioRxiv2024

Genes of the fatty acid oxidation pathway are upregulated in female as compared to male cardiomyocytes

Human females and males differ in cardiac physiology and pathology, even after controlling for sex differences in anthropometrics, lifestyle, and environment. For example, females and males differ in cardiac stroke volume and ventricular thickness, and they exhibit different rates and symptoms of cardiovascular disease. Less is understood about molecular differences in female and male hearts, such as sex differences in gene expression. Here we present an integrative framework utilizing bulk and single-nucleus RNA-sequencing data to study sex differences in the cardiac transcriptome. We show that genes of the fatty acid oxidation (FAO) pathway, the primary source of energy in the heart, are expressed more highly in healthy female than in healthy male hearts. We demonstrate that this sex difference is due to cardiomyocyte-specific, female-biased expression of FAO genes and cannot be explained by sex differences in cardiac cellular composition or number of mitochondria, where FAO takes place. Finally, we observe increased cardiac flux and energetic utilization of free fatty acids in female compared to male hearts. Overall, our results demonstrate that male and female human hearts exhibit fundamental differences in metabolism that likely contribute to sex differences in cardiac physiology and pathology.

genomics↗

bioRxiv2024

Differential prevalence and risk factors for infection with coronaviruses in bats collected during 2020 in Yunnan Province, China

Coronaviruses (CoVs) pose a threat to human health globally, as highlighted by severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the COVID-19 pandemic. Bats from the Greater Mekong Subregion (GMS) are an important natural reservoir for CoVs. Here we report the differential prevalence of CoVs in bats across biological and ecological factors within Yunnan Province. We also show the coexistence of CoVs in individual bats and identify an additional putative host for SARS-related CoV, with higher dispersal capacity than other known hosts. Notably, 11 SARS-related coronaviruses (SARSr-CoVs) were discovered in horseshoe bats and a Chinese water myotis bat by pan-CoV detection and Illumina sequencing. Our findings facilitate an understanding of the fundamental features of the distribution and circulation of CoVs in nature as well as zoonotic spillover risk in the One health framework.

microbiology↗

bioRxiv2024

Artificial Intelligence-Enabled AlphaFold II Pipeline Guides Functional Fluorescence Labeling of Tubulin Across Species

Dynamic properties are essential for microtubule (MT) physiology. Current techniques for in vivo imaging of MTs present intrinsic limitations in elucidating the isotype-specific nuances of tubulins, which contribute to their versatile functions. Harnessing the power of AlphaFold II pipeline, we engineered a strategy for the minimally invasive fluorescence labeling of endogenous tubulin isotypes or those harboring missense mutations. We demonstrated that a specifically designed 16-amino acid linker, coupled with sfGFP11 from the split-sfGFP system and integration into the H1-S2 loop of tubulin, facilitated tubulin labeling without compromising MT dynamics, embryonic development, or ciliogenesis in C. elegans. Extending this technique to human cells and murine oocytes, we visualized MTs with the minimal background fluorescence and a pathogenic tubulin isoform with fidelity. The utility of our approach across biological contexts and species set an additional paradigm for studying tubulin dynamics and functional specificity, with implications for understanding tubulin-related diseases known as tubulinopathies.

cell biology↗

bioRxiv2024

An octopamine-specific GRAB sensor reveals a monoamine relay circuitry that boosts aversive learning

Octopamine (OA), analogous to norepinephrine in vertebrates, is an essential monoamine neurotransmitter in invertebrates that plays a significant role in various biological functions, including olfactory associative learning. However, the spatial and temporal dynamics of OA in vivo remain poorly understood due to limitations associated with the currently available methods used to detect it. To overcome these limitations, we developed a genetically encoded GPCR activation-based (GRAB) OA sensor called GRABOA1.0. This sensor is highly selective for OA and exhibits a robust and rapid increase in fluorescence in response to extracellular OA. Using GRABOA1.0, we monitored OA release in the Drosophila mushroom body (MB), the flys learning center, and found that OA is released in response to both odor and shock stimuli in an aversive learning model. This OA release requires acetylcholine (ACh) released from Kenyon cells, signaling via nicotinic ACh receptors. Finally, we discovered that OA amplifies aversive learning behavior by augmenting dopamine-mediated punishment signals via Oct{beta}1R in dopaminergic neurons, leading to alterations in synaptic plasticity within the MB. Thus, our new GRABOA1.0 sensor can be used to monitor OA release in real-time under physiological conditions, providing valuable insights into the cellular and circuit mechanisms that underlie OA signaling.

neuroscience↗

bioRxiv2024

Development of a LRRC15-Targeted Radio-Immunotheranostic Approach to Deplete Pro-tumorigenic Mechanisms and Immunotherapy Resistance

Leucine-rich repeat containing 15 (LRRC15) has emerged as an attractive biomarker and target for cancer therapy. We have developed a humanized monoclonal antibody (mAb), DUNP19, that specifically binds to a phylogenetically conserved LRRC15 epitope and is internalized by target-expressing cancer and stromal cells. In xenograft mouse models, Lutetium-177 labeled DUNP19 ([177Lu]-DUNP19) enables non-invasive imaging and precise radiotherapy to LRRC15-expressing cancer cells and murine cancer-associated fibroblasts (CAFs), halting tumor progression and prolonging survival with minimal toxicity. Transcriptomic analyses of [177Lu]-DUNP19-treated tumors reveal a loss of pro-tumorigenic mechanisms, including a transforming growth factor beta (TGF{beta})-driven and LRRC15+ signature associated with immunotherapy resistance. Together, these results demonstrate that radio-theranostic targeting of LRRC15 with DUNP19 is a compelling precision medicine platform for image-guided diagnosis, eradication, and reprogramming of LRRC15+ tumor tissue that drives immuno-resistance and aggressive disease. SIGNIFICANCEWe introduce a pioneering LRRC15-guided radio-theranostic approach integrating clinical imaging and radioimmunotherapy. Our strategy utilizes a mAb, DUNP19, to target LRRC15-expressing cancer cells and fibroblasts, demonstrating significant tumor reduction, prolonged survival, and reversal of TGF{beta}-driven treatment resistance. This approach offers a promising strategy for improving outcomes in aggressive cancers.

pharmacology and toxicology↗

bioRxiv2023

Integrated data models on Receptor-Like Kinases for novel domain discovery and functional inference in the plant kingdom

Receptor-like kinases (RLKs) are the largest signal transduction component in plants, determining how different plants adapt to their ecological environment, resulting in plant-specific ecological niches. Current research on RLKs has focused mainly on a small number of typical RLK members of a few model plants. There is an urgent need to study the composition, distribution, and evolution of RLKs at the holistic level to accelerate the understanding of how RLK assists in the ecological adaptation of different plants. In this study, we have collected 528 plant genomes and established an RLK data model, resulting in the discovery and characterization of 524,948 RLK members. Each member is subject to systematic topology classification and coherent gene ID assignment. Using this data model, we discovered two novel families (Xiao and Xiang) of RLKs. Evolutionary analysis of the RLK families indicates that RLCK-XVII and RLCK-XII-2 exist exclusively in dicots, suggesting that the diversification in RLKs between monocots and dicots could cause differences in downstream cytoplasmic responses. We also use interaction proteome to help empower the data mining of inferring new functions of RLK from a global perspective, with the ultimate goal of understanding how RLKs shape the adaptation of different plants to the environment/ecology. The RLK data model compiled herein, together with the annotations and analytic tools, form an integrated data foundation involving multi-omics data and is publicly accessible via the web portal (http://metaRLK.biocloud.top).

bioinformatics↗

bioRxiv2023

In vitro antimicrobial mechanism of diacerein and potential to reverse MRSE resistance to β-lactams

Staphylococcus epidermidis is the most common pathogens causing ocular infection. With the increase of drug resistance rate, it poses a new challenge to anti-infection treatment. In this study, we analyzed the drug resistance of S. epidermidis isolated from the eye in the past 5 years to guide empirical antibiotics treatment. Then, the MIC and MBC of diacerein against MRSE were detected, and continuous induced resistance experiments confirmed that MRSE not easily induce resistance to diacerein. In addition, it was observed that diacerein induced MRSE cell lysis, increased membrane permeability and resulted in intracellular ROS accumulation. Diacerein does not have toxic effects to HCEC at effective bacteriostatic concentrations. The results of checkerboard assay indicated that the combination of diacerein and {beta}-lactams had additive effect on MRSE. We also observed that diacerein may reverse MRSE resistance to {beta}-lactam drugs by affecting the active efflux system. In conclusion, our results provide strong evidence for the high therapeutic potential of diacerein against MRSE.

microbiology↗

bioRxiv2023

Sysrecon: A systematic data-driven tool for genome-scale metabolic reconstructions

Genome-scale metabolic reconstructions contain the information about metabolism, which understands organisms molecular mechanisms better. Different reconstruction procedures are developed to achieve high-quality GSMRs of organisms; however, the descriptions of procedures are vague, meaning that they cannot be qualitatively reproduced, even contradictory, and different published reconstructions may involve different steps. This indicates that there is no unified strategy to quantify the steps in GSMRs. To resolve the problem, we created a R package, Sysrecon, to quantitatively and qualitatively describe the steps of GSMRs in the literature. Sysrecon disassembles GSMR into 93 steps, which are compiled after the comprehensive textual analysis of metabolic reconstructions. Then, Sysrecon decomposes each step of the reconstruction procedure into three components: step content, step conversion, and database and tools. When building a GSMR, Sysrecon creates a template procedure that includes a list of pipeline steps, the description of the information conversion in the steps, and the database and tools that may be used to facilitate the conversion. Because each steps conversion is defined by a formula, the entire GSMR can be dismantled into many step blocks. The reconstruction procedure is therefore transformed into an adaptable automated assembly line that can be customized and tailored to settings of different organisms. To the best of our knowledge, Sysrecon is the first computational tool that dynamically constructs the GSMRs pipeline and provides a framework for defining reconstruction steps and can be used as a basis for the development of high-quality GSMRs.

systems biology↗

bioRxiv2023

Origin and evolution of the bread wheat D genome

Bread wheat (Triticum aestivum) is a globally dominant crop and major source of calories and proteins for the human diet. Compared to its wild ancestors, modern bread wheat shows lower genetic diversity caused by polyploidisation, domestication, and breeding bottlenecks1,2. Wild wheat relatives represent genetic reservoirs, harbouring diversity and beneficial alleles that have not been incorporated into bread wheat. Here, we establish and analyse pangenome resources for Tauschs goatgrass, Aegilops tauschii, the donor of the bread wheat D genome. This new pangenome facilitated the cloning of a disease resistance gene and haplotype analysis across a complex disease resistance locus, allowing us to discern alleles from paralogous gene copies. We also reveal the complex genetic composition and history of the bread wheat D genome, involving previously unreported contributions from genetically and geographically discrete Ae. tauschii subpopulations. Together, our results reveal the complex history of the bread wheat D genome and demonstrate the potential of wild relatives in crop improvement.

genomics↗

bioRxiv2023

Single-cell sequencing for the molecular identity involved in zinc therapy for spinal cord injury

Spinal cord injury (SCI) is a severe traumatic neurological condition often caused by car accidents, violent impacts, or unintentional falls and can have devastating consequences for the patient. SCI include primary and secondary injuries. Followed by primary injury, and secondary injuries including inflammatory responses and oxidative stress, which exacerbate the disease process of SCI. Therefore, the treatment of SCI, especially the suppression of secondary injuries, is a major focus of attention in the field of neuroscience. In previous studies, we have demonstrated that zinc therapy can exert neuroprotective effects in mice after acute SCI, including reducing the inflammatory response in the central nervous system, decreasing the neuronal apoptosis and downregulating oxidative stress at the region of injury. However, little is known about how zinc therapy systematically alleviates SCI. Here, we have systematically analysed and mapped the single-cell atlas of the spinal cord in mice with SCI treated by zinc therapy, which provides a systematic analysis of the transcriptome of individual cells in the spinal cord. Among the results, we found that zinc therapy-induced alterations in the IL-17 inflammatory pathway and produced immune heterogeneity in microglia which are the inherent immune cells in the central nervous system. By cell subpopulations clustering analysis, we defined seven microglia subpopulations in zinc-therapy spinal cord tissue and identified the presence of novel VEGFA+ microglia. This finding presents that the microglia subpopulations affected by zinc therapy may have the potential to promote angiogenesis, which is a potential mechanism for the treatment of SCI. In conclusion, this study maps/reveals the transcriptomic of zinc therapy for the treatment of acute SCI with unprecedented resolution and provides a molecular basis for the clinical application.

genomics↗