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Biology subjects

Xin, Z.

Publications and source records attributed to Xin, Z..

At least 19 recordsLinked to original sources

NRF2 pathway activation and SPP1⁺TREM2⁺ macrophages drive chemoradiotherapy resistance in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is among the most aggressive cancers, with low rates of durable response to chemoradiotherapy and limited therapeutic options for relapsed disease. To uncover mechanisms of treatment resistance and relapse, we performed comprehensive multi-omics profiling of >100 pre-treatment and post-relapse ESCC tumors from a prospective clinical trial (NCT04694391), integrating whole-exome/genome sequencing, bulk RNA-sequencing, single-cell RNA sequencing, and spatial transcriptomics. We identify somatic alterations in NFE2L2/KEAP1 in nearly 40% of relapsed patients, which are associated with upregulation of NRF2 signaling targets in resistant tumors and cell line models. At single-cell and spatial resolution, relapsed tumors are enriched for NRF2-activated epithelial cells that physically co-localize with immunosuppressive SPP1TREM2 macrophages. This co-localization suggests a synergistic interaction between NRF2-driven tumor programs and macrophage-mediated immune suppression that promotes relapse after chemoradiotherapy. Our findings nominate NFE2L2/KEAP1 mutations as predictive biomarkers for patient stratification and highlight therapeutic targeting of NRF2 signaling and SPP1TREM2 macrophages as rational strategies to overcome resistance in ESCC.

cancer biology↗

Leveraging Human Pangenome for Improved Somatic Variant Detection

Somatic variant detection is technically challenging due to low variant allele fractions, the confounding presence of germline variation, and reference bias. Linear references such as GRCh38 miss sample-specific variation, causing misalignments and incorrect variant calls. Although telomere-to-telomere donor-specific assemblies (DSAs) accurately represent individual genomes, their application is limited by cost and technical barriers. Alternatively, the graph-based human pangenome provides a scalable framework to improve read alignment and perform genome inference. Here, we benchmarked somatic variant detection using GRCh38, graph-based pangenomes, and pangenome-inferred DSAs with a HapMap mixture dataset and the COLO829 melanoma cell line. Pangenome-guided alignment improves read mapping and somatic variant calling accuracy. Furthermore, personalized pangenomes partially reconstruct donor-specific genomic content, improving accuracy, reducing germline contamination, and enabling detection of events in loci absent or poorly represented in GRCh38. These findings demonstrate that graph-based and personalized pangenomes are effective strategies for enhancing somatic variant detection compared with GRCh38.

genomics↗

A Pangenomic Method for Establishing a Somatic Variant Detection Resource in HapMap Mixtures

Somatic mosaicism is essential in human biology and disease, yet robust benchmarks are scarce. The SMaHT Consortium mixed six HapMap cell lines to create artificial somatic variants spanning 0.25% to 16.5% variant allele fractions. We developed a technology-agnostic method that builds pangenome graphs from individual assemblies to create unified benchmarking sets: > 6M single-nucleotide variants, 1.8M small insertions/deletions, 49K structural variations, and 10K mobile element insertions across autosomes, X, and mitochondrial chromosomes. We validated the variants using ultra-deep simulated reads and developed a binomial-based model to estimate coverage requirements for variant detection. Evaluating multiple callers showed CHM13 alignment improves structural variant detection and offers advantages in difficult-to-map regions compared to GRCh38. Systematic characterization showed regions with low detection rate are enriched in centromeres, satellite sequences, tandem repeats, and falsely duplicated genes. This accurate, versatile resource enables systematic evaluation of somatic variant detection technologies.

genomics↗

Cross-Platform Omics Pipeline for Integrated Transcriptomics

The fragmentation of single-cell RNA-seq (scRNA-seq) and spatial transcriptomics (ST) tools across Python/R ecosystems, coupled with escalating computational demands for million-cell datasets, creates critical barriers to reproducible analysis. To overcome this, we present CrosPIT (Cross-Platform Omics Pipeline for Integrated Transcriptomics), a cloud-native framework that unifies cross-language analysis in Google Colab with versioned storage on Google Drive. Pre-configured environments enable rapid switching between CPU/GPU/R runtimes, eliminating local hardware constraints. To demonstrate biological utility, we embedded several modules, such as a module for precision detection of malignant epithelial cells in colorectal cancer. CrosPIT thus delivers a scalable, language-agnostic solution that standardizes workflows through native AnnData/Seurat object interoperability, accelerates integrative omics research, and democratizes access to high-performance transcriptomic analysis.

bioinformatics↗

Deciphering of single-cell chromatin accessibility and transcriptome reveals the discrepancy for ex vivo human erythropoiesis

BackgroundErythroid cells can be generated from hematopoietic stem and progenitor cells (HSPC) derived from various sources; however, few studies decode ex vivo human erythropoiesis for the discrepancies at single-cell multi-omics resolution and uncover the underlying restraints for erythrocyte regeneration. ResultsWe deciphered ex vivo human erythropoiesis at two differentiation states from three sources at single-cell chromatin accessibility and transcriptomes level. We identified detrimental myeloid differentiation tendencies during early differentiation. These tendencies were linked to low glutamine activity in cord blood- and iPSC-derived erythropoiesis. The erythroid progenitor differentiation is restricted by cell cycle and hypoxia signaling deficiencies, which are pronounced in the iPSC-derived erythropoiesis. We delineated the erythroid differentiation trajectory of various ex vivo erythropoiesis systems, and revealed a distinct roadmap from HSC to orthochromatic erythroblast with unprecedented resolution. The integrative analysis of single-cell chromatin accessibility and transcriptome across developmental stages uncovered a dynamic coordination, and highlighted the pivotal role of chromatin accessibility and associated enhancers in regulating ex vivo erythropoiesis. Cell-cell communications in the ex vivo erythropoiesis system were not as well established as those in the BM, suggesting that modulating cell-cell communication signals in distinct ex vivo erythropoiesis system may facilitate erythrocyte regeneration. ConclusionsThis study comprehensively characterized the discrepancies and constraints in ex vivo human erythropoiesis at single-cell multi-omics resolution, offering novel strategies to overcome these constraints. These insights are critical for advancing functional erythrocyte generation and have significant implications for clinical applications.

developmental biology↗

EryDB: a transcriptomic profile database for erythropoiesis and erythroid-related diseases

Erythropoiesis is a finely regulated and complex process that involves multiple transformations from hematopoietic stem cells to mature red blood cells at hematopoietic sites from the embryonic to the adult stages. Investigations into its molecular mechanisms have generated a wealth of expression data, including bulk and single-cell RNA sequencing data. A comprehensively integrated and well-curated erythropoiesis-specific database will greatly facilitate the mining of gene expression data and enable large-scale research of erythropoiesis and erythroid related diseases. Here, we present EryDB, an open-access and comprehensive database dedicated to the collection, integration, analysis, and visualization of transcriptomic data for erythropoiesis and erythroid-related diseases. Currently, the database includes expertly curated quality-assured data of 3,803 samples and 1,187,119 single cells derived from 107 public studies of three species (Homo sapiens, Mus musculus, and Danio rerio), nine tissue types, and five diseases. EryDB provides users with the ability to not only browse the molecular features of erythropoiesis between tissues and species, but also perform computational analyses of single-cell and bulk RNA sequencing data, thus serving as a convenient platform for customized queries and analyses. EryDB v1.0 is freely accessible at https://ngdc.cncb.ac.cn/EryDB/home.

bioinformatics↗

Decoding human in vitro terminal erythropoiesis originating from umbilical cord blood mononuclear cells and pluripotent stem cells

Ex vivo RBC production generates unsatisfactory expansion, {beta}-globin expression, and maturation of erythroid cells. The underlying mechanisms behind these limitations and ex vivo terminal erythropoiesis from different origins are largely unexplained. In this study, we mapped an atlas of ex vivo terminally differentiated cells from umbilical cord blood mononuclear cells (UCBMNs) and pluripotent stem cells (PSCs), and observed the differential regulatory dynamics of erythropoiesis from these two origins at a single-cell resolution. We detected the presence of hematopoietic stem progenitor cells (HSPCs), erythroid progenitor (e.g., CFU-E), and non-erythroid cells (e.g., macrophages) in the terminal populations. We observed that UCBMN-derived erythropoiesis is more active than PSC-derived erythropoiesis in terms of the cell cycle, stress erythropoiesis, and autophagy at single cell resolution, which may provide new insights into the limitations in cell expansion, globin expression, and maturation in ex vivo RBC production, respectively. We verified that a stress-erythropoiesis-related gene, TRIB3, increases the expression of globin genes in ex vivo erythropoiesis. As the major unexpected component detected in terminally differentiated cells, CFU-E were further characterized as having high- or low- expansion capacity based on CD99 expression, which generally decreased over erythropoiesis. By inhibiting CD99 gene expression using antagonists, we increased reticulocyte production in the population. Heterogeneous CFU-Es also exist in bone marrow. Moreover, decreased CD99 expression mediates the interactions between macrophages and CFU-E during ex vivo erythropoiesis. Overall, our results provide a reference for facilitating the development of strategies to improve ex vivo RBC regeneration. HighlightsO_LIWe performed scRNA-seq and cell typing of late stage UCBMN- and PSC-derived cells C_LIO_LIStress erythropoiesis, autophagy and cell cycle related gene expression different in two origins C_LIO_LICD99high progenitor cells are a proliferating colony forming unit erythroid subpopulation C_LI

cell biology↗

Avirulent ME49Δgra5 Protecting Hosts Against Toxoplasma gondii Infection and Breast Tumors

Toxoplasma gondii is the causative agent of toxoplasmosis, a zoonotic disease that poses a threat to human health and a considerable loss to livestock farming. At present, clinical therapeutic drugs mainly target T. gondii tachyzoites and fail to eradicate bradyzoites. Developing a safe and effective vaccine against toxoplasmosis is urgent and important. T. gondii possesses dense granule organelles that secrete immunogenic dense granule proteins (GRAs). GRA5 localizes to the parasitophorous vacuole membrane (PVM) in the tachyzoite stage and to the cyst wall in the bradyzoite stage. Here we report that gra5 knockout T. gondii strain is avirulent and fails to form cysts, but stimulates sero-conversion in mice. We next investigated the protective efficacy of ME49{Delta}gra5 vaccination against T. gondii infection. All the immunized mice survived the challenge infection with either wild-type RH, ME49, VEG tachyzoites or ME49 cysts. Remarkably, ME49{Delta}gra5 tachyzoites inoculation in situ attenuated the growth of murine breast tumor (4T1) in mice and prevented 4T1s lung metastasis. ME49{Delta}gra5 inoculation might upregulate the levels of Th1 cytokines and tumor-infiltrating T cells in tumor microenvironment (TME) and trigger anti-tumor responses by increasing the number of NK, B, T cells, macrophages, and dendritic cells (DCs) in spleen. Collectively, the results support the potential of ME49{Delta}gra5 as attenuated live vaccine against T. gondii infection and breast cancer. Author summaryThe zoonotic toxoplasmosis poses a great disease burden to humans and big loss to livestock farming. At present, clinical therapeutic drugs mainly target T. gondii tachyzoites but have no effect on bradyzoites. A safe and effective vaccine against toxoplasmosis is urgent and important. Dense granule proteins (GRAs) are a group of immunoactive proteins secreted by T. gondii dense granule organelles. GRA5 is located on the parasitophorous vacuole membrane (PVM) at the tachyzoite stage and on the cyst wall at the bradyzoite stage. We discovered that the gra5 knockout T. gondii strain became avirulent and failed to form cysts in mice. ME49{Delta}gra5 immunized mice survived the challenge infection of wild-type RH, ME49, and VEG tachyzoites, and ME49 cysts. Meanwhile, ME49{Delta}gra5 tachyzoites inoculation in situ remarkably attenuated the growth of murine breast tumor (4T1) in mice including the injected and distant tumors, as well as prevented 4T1s lung metastasis. This results support the potential of ME49{Delta}gra5 as attenuated live vaccine against T. gondii infection and breast cancer.

microbiology↗

IRE-1α is a key switch of pyroptosis and necroptosis in mice by dominating Gasdermin D

Necroptosis and pyroptosis are lytic and inflammatory types of programmed cell death that require the membrane destruction predominantly driven by the mixed lineage kinase domain-like (MLKL) and gasdermin D (GSDMD) proteins, respectively. However, the crosstalk between them remains largely unknown. Here, our research discloses that endoplasmic reticulumn transmembrane protein inositol-requiring enzyme-1 (IRE-1) is a potential modulator of both necroptosis and pyroptosis, paricularly in liver pathology. Interestingly, enhanced expression of IRE-1 triggers hepatic pyroptosis, while defective IRE-1 level activates hepatic necroptosis, and both processes are closed related to the activity of GSDMD in mice. To elucidate unknown crosstalk, by using pharmacological and genetic methods, we first demonstrated that IRE-1 suppresses necroptosis by promoting the expression of GSDMD and cleaves caspase-8 and by inhibiting the expression of receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3 and MLKL. Unexpectedly, excess IRE-1 initiates pyroptosis by increasing GSDMD and NLRP3 levels. Our work clearly provides insight into the modulation of IRE-1 to dominate necroptosis and pyroptosis and suggests that IRE-1 may be a promising therapeutic target for drug discovery in both types of tissue injuries.

cell biology↗

Oxidative phosphorylation pathway disruption is an alternative pathological mechanism leading to Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA) is a rare congenital disorder characterized by the failure of erythroid progenitor differentiation; however, the molecular mechanisms leading to erythroid defects remain unclear. By analyzing the transcriptomic profiles of bone marrow from patients with DBA (n = 10), we identified the dysfunction of the oxidative phosphorylation (OXPHOS) pathway as a possible cause of DBA. We established a DBA cell model using differentiating hematopoietic stem progenitor cells in which the OXPHOS pathway was suppressed to completely recapitulate the defects in erythroid progenitor differentiation, ribosome biogenesis, and heme biosynthesis, which are representative characteristics of patients with DBA. Disruption of the OXPHOS pathway led to ribosomal defects and associated erythroid defects via abolishment of the Ran GTPase activating protein RanGAP1, which is pivotal in the RNA transport pathway. The composition of the ribosomal proteins in the established DBA cells was unchanged, but an overall reduction in ribosomal protein levels was observed, leading to an alteration in the translation of a subset of transcripts specific to erythropoiesis. We revealed that the OXPHOS pathway participates in erythropoiesis, particularly at an early stage, and reinforced the relationship between the OXPHOS pathway and erythropoiesis. Coenzyme Q10, an activator of OXPHOS, largely rescued the erythroid defects in DBA cells. Our results reveal that OXPHOS repression is an alternative pathological mechanism leading to DBA, demonstrating its potential as a therapeutic pathway. Key PointsO_LIOxidative phosphorylation (OXPHOS) pathway disruption is an alternative pathological mechanism underlying Diamond-Blackfan anemia (DBA). C_LIO_LISuppression of OXPHOS leads to defects in erythropoiesis and ribosomal biogenesis via the RanGAP1 protein. C_LI

cell biology↗

Mapping of single-cell landscape of acral melanoma and analysis of molecular regulatory network of tumor microenvironment

Melanoma is a type of skin malignant tumor with high invasiveness, high metastasis, and poor prognosis. The incidence of melanoma continues to increase. Among them, the subtype of acral melanoma (AM) is more common in Asian populations. AM has higher degree, low immunotherapy response rate. With the help of single-cell sequencing technology provides new technical means for tumor microenvironment research, so that we can more easily explore specific tumor types suitable immunotherapy targets. However, no complete single-cell level differentiation map exists for the AM tumor microenvironment (TME). In this study, we used AM related sample and used the 10x Genomics single-cell transcriptome platform to draw a specific single-cell map of AM, understand the cell composition of AM, and analyze the interaction and molecular regulation of AM TME. Nine cell types were identified, of which malignant cells accounted for the largest proportion, followed by fibroblasts. And the cell interaction network shows that malignant cells, macrophages, B, T and fibroblasts play an important role in AM TME. Our research provides systematic theoretical guidance for the diagnosis and treatment of acral melanoma.

genomics↗

Construction of competing endogenous RNA interaction networks as prognostic markers in metastatic melanoma

Malignant melanoma (MM) is a highly aggressive, metastatic cancer originating from melanocytes. These tumors have an extremely poor prognosis. MM accounts for 4% of skin cancers with an 80% mortality rate. The median survival of patients with metastatic melanoma is approximately six months, with a five-year survival rate of less than 10%. In recent years, the incidence of melanoma has gradually increased and has become one of the deadliest cancers. Competitive endogenous RNA (ceRNA) models the mechanism by which long chain non-coding RNAs (lncRNAs) play a regulatory role in the disease. LncRNAs can act as a sponge, competitively attracting small RNAs (micoRNAs; miRNAs) and interfering with miRNA function. This can affect the expression of target gene messenger RNAs (mRNAs), ultimately promoting tumorigenesis and tumor progression. Bioinformatics analysis may identify potentially prognostic and therapeutically-relevant differentially expressed genes in MM, as well as lncRNAs, miRNAs and mRNAs that are interconnected through the ceRNA network. This may provide further insight into gene regulation and the prognosis of metastatic melanoma. Weighted co-expression networks were used to identify lncRNA and mRNA modules associated with the metastatic phenotype, as well as the co-expression genes contained in the modules. We used 17 lncRNAs, six miRNAs, and 11 mRNAs to construct a ceRNA interaction network with a regulatory role in patients with metastatic melanoma. The prognostic risk model was used as a sorter to classify the survival prognosis of melanoma patients. Four groups of ceRNA interaction triplets were obtained, and miR-3662 may be used in the treatment of metastatic melanoma patients. Experiments confirmed the regulating relationship and phenotype of this assumption. This study provides new targets to regulate the metastatic process, predict metastatic potential and determine that miR-3662 may be used in the treatment of melanoma.

cancer biology↗

Pan-genome Analysis in Sorghum Highlights the Extent of Genomic Variation and Sugarcane Aphid Resistance Genes

Sorghum bicolor, one of the most important grass crops around the world, harbors a high degree of genetic diversity. We constructed chromosome-level genome assemblies for two important sorghum inbred lines, Tx2783 and RTx436. The final high-quality reference assemblies consist of 19 and 18 scaffolds, respectively, with contig N50 values of 25.6 and 20.3 Mb. Genes were annotated using evidence-based and de novo gene predictors, and RAMPAGE data demonstrate that transcription start sites were effectively captured. Together with other public sorghum genomes, BTx623, RTx430, and Rio, extensive structural variations (SVs) of various sizes were characterized using Tx2783 as a reference. Genome-wide scanning for disease resistance (R) genes revealed high levels of diversity among these five sorghum accessions. To characterize sugarcane aphid (SCA) resistance in Tx2783, we mapped the resistance region on chromosome 6 using a recombinant inbred line (RIL) population and found a SV of 191 kb containing a cluster of R genes in Tx2783. Using Tx2783 as a backbone, along with the SVs, we constructed a pan-genome to support alignment of resequencing data from 62 sorghum accessions, and then identified core and dispensable genes using this population. This study provides the first overview of the extent of genomic structural variations and R genes in the sorghum population, and reveals potential targets for breeding of SCA resistance.

genomics↗

MonaGO: a novel Gene Ontology enrichment analysis visualisation system

MonaGO is a novel web-based visualisation system that provides an intuitive, interactive and responsive interface for performing gene ontology (GO) enrichment analysis and visualising the results. MonaGO combines dynamic clustering and interactive visualisation as well as customisation options to assist biologists in obtaining meaningful representation of overrepresented GO terms, producing simplified outputs in an unbiased manner. MonaGO supports gene lists as well as GO terms as inputs. Visualisation results can be exported as high-resolution images or restored in new sessions, allowing reproducibility of the analysis. An extensive comparison between MonaGO and 11 state-of-the-art GO enrichment visualisation tools based on 9 features revealed that MonaGO is the only platform that simultaneously allows interactive visualisation within one single output page, directly accessible through a web browser with customisable display options. In summary, MonaGO will facilitate the interpretation of GO analysis and will assist the biologists into the representation of the results.

bioinformatics↗

COMPOSITUM 1 (COM1) contributes to the architectural simplification of barley inflorescence via cell wall-mediated and meristem identity signals

Grasses have varying inflorescence shapes; however, little is known about the genetic mechanisms specifying such shapes among tribes. We identified the grass-specific TCP transcription factor COMPOSITUM 1 (COM1) expressed in inflorescence meristematic boundaries of different grasses. COM1 specifies branch-inhibition in Triticeae (barley) versus branch-formation in non-Triticeae grasses. Analyses of cell size, cell walls and transcripts revealed barley COM1 regulates cell growth, affecting cell wall properties and signaling specifically in meristematic boundaries to establish identity of adjacent meristems. COM1 acts upstream of the boundary gene Liguleless1 and confers meristem identity partially independent of the COM2 pathway. Furthermore, COM1 is subject to purifying natural selection, thereby contributing to specification of the spike inflorescence shape. This meristem identity pathway has conceptual implications for both inflorescence evolution and molecular breeding in Triticeae.

plant biology↗

Mapping Human Pluripotent Stem Cell Derived Erythroid Differentiation by Single-Cell Transcriptome Analysis

There is an imbalance between the supply and demand of functional red blood cells (RBCs) in clinical applications. This imbalance can be addressed by regenerating RBCs using several in vitro methods. Induced pluripotent stem cells (iPSCs) can handle the low supply of cord blood and the ethical issues in embryonic stem cell research and provide a promising strategy to eliminate immune rejection. However, no complete single-cell level differentiation pathway exists for the iPSC-derived RBC differentiation system. In this study, we used iPSC line BC1 to establish a RBCs regeneration system. The 10x genomics single-cell transcriptome platform was used to map the cell lineage and differentiation trajectories on day 14 of the regeneration system. We observed that iPSCs differentiation was not synchronized during embryoid body (EB) culture. The cells (day 14) mainly consisted of mesodermal and various blood cells, similar to the yolk sac hematopoiesis. We identified six cell classifications and characterized the regulatory transcription factors (TFs) networks and cell-cell contacts underlying the system. iPSCs undergo two transformations during the differentiation trajectory, accompanied by the dynamic expression of cell adhesion molecules and estrogen-responsive genes. We identified different stages of erythroid cells such as burst-forming unit erythroid (BFU-E) and orthochromatic erythroblasts (ortho-E) and found that the regulation of TFs (e.g., TFDP1 and FOXO3) is erythroid-stage specific. Immune erythroid cells were identified in our system. This study provides systematic theoretical guidance for optimizing the iPSCs-derived RBCs differentiation system, and this system is a useful model for simulating in vivo hematopoietic development and differentiation.

developmental biology↗

Fertility of Pedicellate Spikelets in Sorghum is Controlled by a Jasmonic Acid Regulatory Module

As in other cereal crops, the panicles of sorghum (Sorghum bicolor (L.) Moench) comprise two types of floral spikelets (grass flowers). Only sessile spikelets (SSs) are capable of producing viable grains, whereas pedicellate spikelets (PSs) cease development after initiation and eventually abort. Consequently, grain number per panicle (GNP) is lower than the total number of flowers produced per panicle. The mechanism underlying this differential fertility is not well understood. To investigate this issue, we isolated a series of EMS-induced multiseeded (msd) mutants that result in full spikelet fertility, effectively doubling GNP. Previously, we showed that MSD1 is a TCP (Teosinte branched/Cycloidea/PCF) transcription factor that regulates jasmonic acid (JA) biosynthesis, and ultimately floral sex organ development. Here, we show that MSD2 encodes a lipoxygenase (LOX) that catalyzes the first committed step of JA biosynthesis. Further, we demonstrate that MSD1 binds to the promoters of MSD2 and other JA pathway genes. Together, these results show that a JA-induced module regulates sorghum panicle development and spikelet fertility. The findings advance our understanding of inflorescence development and could lead to new strategies for increasing GNP and grain yield in sorghum and other cereal crops.\n\nSignificanceThrough a single base pair mutation, grain number can be increased by ~200% in the globally important crop Sorghum bicolor. This mutation affects the expression of an enzyme, MSD2, that catalyzes the jasmonic acid pathway in developing floral meristems. The global gene expression profile in this enzymatic mutant is similar to that of a transcription factor mutant, msd1, indicating that disturbing any component of this regulatory module disrupts a positive feedback loop that occurs normally due to regular developmental perception of jasmonic acid. Additionally, the MSD1 transcription factor is able to regulate MSD2 in addition to other jasmonic acid pathway genes, suggesting that it is a primary transcriptional regulator of this hormone signaling pathway in floral meristems.

plant biology↗

GIGANTEA promotes sorghum flowering by stimulating floral activator gene expression

iv. FundingThis work was supported by USDA-ARS CRIS projects 2030-21000-039-00D and 2030-21000-049-00D to F.G.H.\n\nv. AbstractThe C4 grass Sorghum bicolor is an important grain and subsistence crop, animal forage, and cellulosic biofuel feedstock that is tolerant of abiotic stresses and marginal soils. Sorghum is short-day flowering, an obstacle for adaptation as a grain crop but a benefit as a biofuel feedstock. To identify genes underlying sorghum photoperiodic flowering behavior this study characterized the Sbgi-ems1 nonsense mutation in the sorghum GIGANTEA (SbGI) gene from a sequenced M4 EMS-mutagenized BTx623 population. Sbgi-ems1 plants had reduced stature and leaf blades exhibiting increased lateral growth combined with reduced proximal-distal growth. Mutant plants flowered later than normal siblings under long-day conditions provided by greenhouse or field. Delayed flowering in Sbgi-ems1 plants accompanied by an increase in internode number, indicating an extended vegetative growth phase prior to flowering. Sbgi-ems1 plants had reduced expression of floral activator genes SbCO and SbEhd1 and downstream FT-like florigen genes SbFT, SbCN8, and SbCN12. Therefore, SbGI accelerates flowering by promotion of SbCO and SbEhd1 expression. Circadian clock-associated genes SbTOC1 and SbLHY had disrupted expression in Sbgi-ems1 plants. This work demonstrates SbGI is a key upstream activator in the regulatory networks dictating sorghum flowering time and growth, as well as gene expression regulation within the circadian clock.\n\nSummary StatementSorghum GIGANTEA contributes to flowering time, growth, and the circadian clock with activities opposite to its maize homolog. GI occupies a conserved position within regulatory networks but has plastic activity.

plant biology↗