Biology subjects

Kang, Y.

Publications and source records attributed to Kang, Y..

At least 73 records · Page 4Linked to original sources

bioRxiv2022

Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups

We present 4,157 whole-genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest whole genomic resource of Koreans. Korea4K provides 45,537,252 variants and encompasses most of the common and rare variants in Koreans. We identified 1,356 new geno-phenotype associations which were not found by the previous Korea1K dataset. Phenomics analyses revealed 24 genetic correlations, 1,131 pleiotropic variants, and 127 causal relationships from Mendelian randomization. Moreover, the Korea4K imputation reference panel showed a superior imputation performance to Korea1K. Collectively, Korea4K provides the most extensive genomic and phenomic data resources for discovering clinically relevant novel genome-phenome associations in Koreans.

genomics↗

bioRxiv2022

Single-cell profiling uncovers a Muc4-expressing metaplastic gastric cell type sustained by Helicobacter pylori-specific inflammation

AbstractMechanisms for Helicobacter pylori (Hp)-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant Hp infection and induction of constitutively active KRAS (Hp+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA-seq showed that Hp+KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin Muc4 and the growth factor amphiregulin. Metaplastic pit cells were associated with macrophage and T cell inflammation and prevented by gastric immunosuppression. Lineage tracing showed that Muc4 was not dependent on cell-intrinsic KRAS activity, and lineage-derived cells had a limited propensity for growth as organoids, demonstrating that metaplastic pit cells are largely not self- renewing. Finally, MUC4 expression was significantly associated with proliferation in human gastric cancer samples. These studies identify an Hp-associated metaplastic pit cell lineage, also found in human gastric cancer tissues, whose expansion is driven by Hp-dependent inflammation. Statement of SignificanceUsing a mouse model, we have delineated metaplastic pit cells as a pre-cancerous cell type whose expansion requires H. pylori-driven inflammation. In humans, metaplastic pit cells show enhanced proliferation as well as enrichment in precancer and early cancer tissues, highlighting an early step in the gastric metaplasia to cancer cascade.

microbiology↗

bioRxiv2022

FMRP phosphorylation modulates neuronal translation through YTHDF1

Translation activation of local synaptic mRNAs is critical to learning and memory1-3. Despite extensive studies on how phosphorylation of ribosomal proteins and translation factors enables timely response to exogenous stimuli4, our knowledge on molecular pathways utilized by RNA binding proteins (RBPs) to control translation of specific mRNAs remains incomplete. We have previously found that YTHDF1 regulates depolarization-induced protein synthesis by promoting translation of N6-methyladenosine (m6A)-modified transcripts5. Here we report an unexpected mechanism that the stimuli-induced neuronal translation is mediated by phosphorylation of a YTHDF1-binding protein FMRP. Phosphorylation of FMRP serine 499 induced by neuronal depolarization alters the condensing behavior of prion-like protein YTHDF1. Unphosphorylated FMRP sequesters YTHDF1 away from the translation initiation complex, whereas the stimulation-induced FMRP phosphorylation releases YTHDF1 to form translational active condensates with the ribosome to activate translation of YTHDF1 target transcripts. In fragile X syndrome (FXS) models characterized by low FMRP expression, we observed YTHDF1-mediated hyperactive translation, which notably impacts FXS pathophysiology. Developmental defects in an FXS forebrain organoid model could be reversed by a selective small-molecule inhibitor of YTHDF1 which acts by suppressing its condensation in neurons. We characterized transcriptome-wide mRNA translation with inhibitor treatment in organoids and identified targets that explain alleviated FXS pathology. Our study thus reveals FMRP and its phosphorylation as an important regulator of the activity-dependent translation during neuronal development and stimulation, and identifies YTHDF1 as a potential therapeutic target for FXS in which developmental defects caused by FMRP depletion could be reversed through YTHDF1 inhibition.

molecular biology↗

bioRxiv2022

A Fast Solution for Automated Single-Molecule Force Spectroscopy Data Collection and Processing

Force spectroscopy is a sophisticated technology for studying the physical chemistry of polymers at the single-molecule level. Its implication in biomolecules, e.g., proteins, DNA or RNA, yielded tremendous information on their structures, folding, and functions. In a routine procedure, an experimenter pulls the molecule of interest to generate the force-extension (FE) curve using technologies that include atomic force microscopy (AFM), magnetic force spectroscopy (MFS), optical tweezer and acoustic force spectroscopy (AFS), then extract parameters characteristic to the polymer. The latter step requires fitting the FE curve with mathematical models. Although several models have been widely applied for over 20 years, the fitting of the experimental data was not as straightforward. This step can be time-consuming, prone to mistakes, and sometimes cause debate. To lower the technical barriers for users and to reduce the time consumption and errors involved in force spectroscopy data processing, we optimized the fitting procedure for three classical worm-like chain (WLC) models into an automated software package named Single Molecule Force Spectroscopy Toolkit (SMFST). Our MATLAB-based software with a graphical user interface demonstrated robust fitting for three models in a wide range of forces and provided convenient tools for batch data processing to meet future requirements of high-throughput data collection.

biophysics↗

bioRxiv2022

The Tre1/S1pr1 phospholipid-binding G protein-coupled receptor signaling pathway is required for astrocyte morphogenesis

Astrocytes play crucial roles in regulating neural circuit function by forming a dense network of synapse-associated membrane specializations, but signaling pathways regulating astrocyte morphogenesis remain poorly defined. Here we show the Drosophila lipid-binding G protein-coupled receptor (GPCR) Tre1, likely acting through Rac1, is required for astrocytes to elaborate their complex morphology in vivo. The lipid phosphate phosphatases Wunen/Wunen2, which process phospholipid ligands, also regulate astrocyte morphology, and, via Tre1, mediate astrocyte-astrocyte competition for growth promoting lipids. Loss of s1pr1, the functional analog of Tre1 in zebrafish disrupts astrocyte process elaboration. Live-imaging and pharmacology demonstrate that S1pr1 balances proper astrocyte process extension/retraction dynamics during morphogenesis, and that S1pr1 signaling is required throughout astrocyte development. Tre1 and S1pr1 are thus potent evolutionarily conserved regulators of astrocyte growth and elaboration of morphological complexity. O_LIThe GPCR Tre1 and LPPs Wun/Wun2 promote astrocyte process outgrowth in Drosophila C_LIO_LIAstrocytes compete for a growth{-}promoting phospholipid in the CNS C_LIO_LIWun/Wun2 act locally to regulate process outgrowth through Tre1 C_LIO_LIVertebrate S1pr1 regulates astrocyte growth early, through modulation of process dynamics C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/508188v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1e86db5org.highwire.dtl.DTLVardef@7abd6borg.highwire.dtl.DTLVardef@29f163org.highwire.dtl.DTLVardef@1a6c4b9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Nardilysin-Regulated Scission Mechanism Activates Polo-like Kinase 3 to Suppress the Development of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of apoptotic pathways. Here, we find that development of anoikis resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often reduced Plk3 expression in human PDAC. Importantly, a 41 kDa Plk3 (p41Plk3) that contained the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase Nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) was quickly removed by proteasome degradation preventing the p41Plk3 inhibition by PBD. We found that p41Plk3 is the activated form of Plk3 that regulates a feedforward mechanism to promote anoikis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn, induces expression of Plk3 and pro-apoptotic genes. These findings uncovered an NRDC-regulated post-translational mechanism (PTM) that activates Plk3, establishing a prototypic regulation by scission mechanism.

cancer biology↗

bioRxiv2022

Chromatin Remodeling in Patient-Derived Colorectal Cancer Models

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, we compared the transcriptomic and chromatin accessibility landscapes of six matched sets of colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) and discovered two major remodeling axes. The first axis delineates PDX and PDO from PT, and the second axis distinguishes PDX and PDO. PDOX were more similar to PDX than they were to PDO, indicating that the growth environment is a driving force for chromatin adaptation. Using bivariate genomic footprinting analysis, we identified transcription factors (TF) that differentially bind to open chromatins between matched PDO and PDOX. Among them, KLF14 and EGR2 footprints were enriched in all six PDOX relative to matched PDO, and silencing of KLF14 or EGR2 promoted tumor growth. Furthermore, EPHA4, a shared downstream target gene of KLF14 and EGR2, altered tumor sensitivity to MEK inhibitor treatment. Altogether, patient-derived CRC cells undergo both common and distinct chromatin remodeling in PDO and PDX/PDOX, driven largely by their respective microenvironments, which results in differences in growth and drug sensitivity and needs to be taken into consideration when interpreting their ability to predict clinical outcome.

cancer biology↗

bioRxiv2022

Identification of ASPDH as a novel NAADP-binding protein

NAADP is a signaling molecule that can induce calcium release from intracellular acidic stores. However, proteins that bind to NAADP are understudied. Here, we identify ASPDH as an NAADP-binding protein through biochemical purification from pig livers. ITC experiment using the recombinantly expressed protein shows a 1:1 binding stoichiometry and a Kd of 455 nM between NAADP and mouse ASPDH. In contrast, recombinantly expressed JPT2 and LSM12, two proteins previously identified as NAADP-receptors, show no binding in ITC experiments.

biochemistry↗

bioRxiv2022

Cilia regulate meiotic recombination in zebrafish

Meiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been extensively investigated. However, it is still unclear whether signals from the cytoplasm or even outside of the cell can regulate the meiosis process. Cilia are microtubule-based structures that protrude from cell surface and function as signaling hubs to sense extracellular signals. Here, we reported an unexpected and critical role of cilia during meiotic recombination. During gametogenesis of zebrafish, cilia were specifically present in the prophase stages of both spermatocytes and primary oocytes. By developing a novel germ cell-specific CRISPR/Cas9 system, we demonstrated that germ cell-specific depletion of ciliary genes resulted in compromised double strand break repair, reduced crossover formation, and increased germ cell apoptosis. Our study reveals a previously undiscovered role for cilia during meiosis and suggests that extracellular signals may regulate meiotic recombination via this particular organelle.

developmental biology↗

bioRxiv2022

The circ_0002538/miR-138-5p/PLLP axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, but the underlying molecular pathogenesis remains unclear. Accumulating evidence indicates that circular RNAs (circRNAs) play vital roles in DPN, while their expressions and functions in Schwann cell (SC) are rarely reported. Here, we performed protein profiling and circRNA sequencing on the peripheral nerves of patients with or without DPN. A total of 265 differentially expressed proteins were identified in DPN by protein profiling, which mainly enrich in myelination according to Gene Ontology analysis. Further, 15637 circRNAs were identified by circRNA sequencing, of which 11 were verified to be dysregulated. Among them, circ_0002538 was found to be downregulated in DPN and chosen for further investigation. Functional experiments revealed that circ_0002538 overexpression promoted SC migration and relieved demyelination in DPN. Mechanistic studies revealed that circ_0002538 could promote PLLP expression by sponging miR-138-5p, while lack of circ_0002538 led to PLLP deficiency, which further suppressed SC migration and caused demyelination. The present research provided novel insights into the pathogenesis of DPN, in which the circ_0002538/miR-138-5p/PLLP axis was suppressed in SCs and hence caused demyelination. These findings expanded the role of circRNAs in DPN and provided potential therapeutic targets for DPN.

neuroscience↗

bioRxiv2021

Structure and mechanism of NALCN-FAM155A-UNC79-UNC80 channel complex

NALCN channel mediates sodium leak currents and is important for maintaining proper resting membrane potential. NALCN and FAM155A form the core complex of the channel, the activity of which essentially depends on the presence of both UNC79 and UNC80, two auxiliary proteins. NALCN, FAM155A, UNC79, and UNC80 co-assemble into a large hetero-tetrameric channel complex. Genetic mutations of NALCN channel components lead to neurodevelopmental diseases. However, the structure and mechanism of the intact channel complex remain elusive. Here, we present the cryo-EM structure of the mammalian NALCN-FAM155A-UNC79-UNC80 quaternary complex. The structure showed that UNC79-UNC80 form a large piler-shaped heterodimer which was tethered to the intracellular side of the NALCN channel through tripartite interactions with the cytoplasmic loops of NALCN. Two interactions are essential for proper cell surface localization of NALCN. The other interaction relieves the self-inhibition of NALCN by pulling the auto-inhibitory CTD Interacting Helix (CIH) out of its binding site.

biophysics↗

bioRxiv2021

Physiological and genetic drivers underpinning canopy development are associated with durum wheat yield in rainfed environments

New durum wheat (Triticum turgidum L. ssp. Durum) cultivars with improved adaptation to variable rainfall environments are required to sustain productivity in the face of climate change. Physiological traits related to canopy development underpin the production of biomass and yield, as they interact with solar radiation and affect the timing of water use throughout the growing season. This study explored the temporal canopy dynamics of durum wheat using a nested-association mapping population evaluated for longitudinal normalized difference vegetation index (NDVI) measurements. Association mapping was performed to identify quantitative trait loci (QTL) for time-point NDVI and spline-smoothed NDVI trajectory traits. Yield effects associated with QTL for canopy development were investigated using data from four rainfed field trials. Four QTL associated with slower canopy closure, improved yield in specific environments, and notably, were not associated with a yield penalty in any environment. This was likely due to optimised timing of water-use and pleiotropic effects on yield component traits, including spike number and spike length. Overall, this study suggests that slower canopy closure is beneficial for durum wheat production in rainfed environments. Selection for traits or loci associated with canopy development may improve yield stability of durum wheat in water limited environments.

genetics↗

bioRxiv2021

Calcium/Calmodulin Dependent Protein Kinase Kinase 2 Regulates the Expansion of Tumor-induced Myeloid-Derived Suppressor Cells

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells, which can suppress the immune response, promote tumor progression and impair the efficacy of immunotherapies. Consequently, the pharmacological targeting of MDSC is emerging as a new immunotherapeutic strategy to stimulate the natural anti-tumor immune response and potentiate the efficacy of immunotherapies. Herein, we leveraged genetically modified models and a small molecule inhibitor to validate Calcium-Calmodulin Kinase Kinase 2 (CaMKK2) as a druggable target to control MDSC accumulation in tumor-bearing mice. The results indicated that deletion of CaMKK2 in the host attenuated the growth of engrafted tumor cells, and this phenomenon was associated with increased antitumor T cell response and decreased accumulation of MDSC. The adoptive transfer of MDSC was sufficient to restore the ability of the tumor to grow in Camkk2-/- mice, confirming the key role of MDSC in the mechanism of tumor rejection. In vitro studies indicated that blocking of CaMKK2 is sufficient to impair the yield of MDSC. Surprisingly, MDSC generated from Camkk2-/- bone marrow cells also showed a higher ability to terminally differentiate toward more immunogenic cell types (e.g inflammatory macrophages and dendritic cells) compared to wild type (WT). Higher intracellular levels of reactive oxygen species (ROS) accumulated in Camkk2-/- MDSC, increasing their susceptibility to apoptosis and promoting their terminal differentiation toward more mature myeloid cells. Mechanistic studies indicated that AMP-activated protein kinase (AMPK), which is a known CaMKK2 proximal target controlling the oxidative stress response, fine-tunes ROS accumulation in MDSC. Accordingly, failure to activate the CaMKK2-AMPK axis can account for the elevated ROS levels in Camkk2-/- MDSC. These results highlight CaMKK2 as an important regulator of the MDSC lifecycle, identifying this kinase as a new druggable target to restrain MDSC expansion and enhance the efficacy of anti-tumor immunotherapy.

immunology↗

bioRxiv2021

Dual functions of ZmGI1 in the photoperiodic flowering pathway and salt stress responses in maize

The circadian clock perceives photoperiodic changes and initiates processes leading to floral transition. GIGANTEA (GI) primarily functions as a principal clock component that integrates environmental cues into regulation of growth and development in Arabidopsis. However, it is unclear whether ZmGIs regulate photoperiodic flowering and abiotic stress response. Here, we demonstrated that the expression of ZmGI1 depicted a typical circadian pattern and was differentially expressed under LDs and SDs in photoperiodic sensitive and insensitive maize lines. The transcription level was significantly and positively correlated with days to silking and photoperiodic sensitivity in maize. Moreover, natural variation in ZmGI1 was associated with maize photoperiod response and the fine-tuning of plant development traits. Overexpression of ZmGI1Huangzao4 induced early flowering and enhanced salt tolerance in Arabidopsis relative to the wild-type and gi mutants. ZmGI1 formed a protein complex with ZmFKF1 and acted as a positive regulator of flowering time by regulating CONSTANS transcription in the photoperiod pathway. The ZmGI1/ZmThox complex regulates oxidative stress induced by salt stress via a redox balance pathway. Over all, we have provided compelling evidence to suggest that ZmGI1 is a pleotropic gene whose expression depicts a typical circadian rhythmic pattern and regulates flowering time and confers salt stress tolerance.

developmental biology↗

bioRxiv2021

Strategic infarct locations for post-stroke depressive symptoms: a lesion- and disconnection-symptom mapping study

BackgroundDepression is the most common neuropsychiatric complication after stroke. Infarct location is associated with post-stroke depressive symptoms (PSDS), but it remains debated which brain structures are critically involved. We performed a large-scale lesion-symptom mapping study to identify infarct locations, and white matter disconnections, associated with PSDS. MethodsWe included 553 patients (age 69{+/-}11 years, 42% female) with acute ischemic stroke. PSDS were measured using the 30-item Geriatric Depression Scale (GDS-30). Multivariable support vector regression (SVR)-based analyses were performed both at the level of individual voxels (SVR-VLSM) and predefined regions of interest (SVR-ROI) to relate infarct location to PSDS. We externally validated our findings in an independent stroke cohort (N=459). Finally, disconnectome-based analyses were performed using SVR-VLSM, in which white matter fibers disconnected by the infarct were analyzed instead of the infarct itself. Results: Infarcts in the right amygdala, right hippocampus and right pallidum were consistently associated with PSDS (permutation-based p<0.05) in SVR-VLSM and SVR-ROI. External validation (N=459) confirmed the association between infarcts in the right amygdala and pallidum, but not the right hippocampus, and PSDS. Disconnectome-based analyses revealed that disconnections in the right parahippocampal white matter, right thalamus and pallidum, and right anterior thalamic radiation were significantly associated (permutation-based p<0.05) with PSDS. ConclusionsInfarcts in the right amygdala and pallidum, and disconnections of right limbic and frontal cortico-basal ganglia-thalamic circuits, are associated with PSDS. Our findings provide a comprehensive and integrative picture of strategic infarct locations for PSDS, and shed new light on pathophysiological mechanisms of depression after stroke.

neuroscience↗

bioRxiv2021

MSH2-MSH3 promotes DNA end resection during HR and blocks TMEJ through interaction with SMARCAD1 and EXO1

DNA double strand break (DSB) repair by Homologous recombination (HR) is initiated by the end resection, a process during which 3 ssDNA overhangs are generated by the nucleolytic degradation. The extent of DNA end resection determines the choice of the DSB repair pathway. The role of several proteins including nucleases for end resection has been studied in detail. However, it is still unclear how the initial, nicked DNA generated by MRE11-RAD50-NBS1 is recognized and how subsequent proteins including EXO1 are recruited to DSB sites to facilitate extensive end resection. We found that the MutS{beta} (MSH2-MSH3) mismatch repair (MMR) complex is recruited to DSB sites by recognizing the initial nicked DNA at DSB sites through the interaction with the chromatin remodeling protein SMARCAD1. MSH2-MSH3 at DSB sites helps to recruit EXO1 for long-range resection and enhances its enzymatic activity. MSH2-MSH3 furthermore inhibits the access of DNA polymerase {theta} (POLQ), which promotes polymerase theta-mediated end-joining (TMEJ) of DSB. Collectively, our data show a direct role for MSH2-MSH3 in the initial stages of DSB repair by promoting end resection and influencing DSB repair pathway by favoring HR over TMEJ. Our findings extend the importance of MMR in DSB repair beyond established role in rejecting the invasion of sequences not perfectly homologous to template DNA during late-stage HR.

molecular biology↗

bioRxiv2021

An ELISA-based method for rapid genetic screens in Drosophila

Drosophila is a powerful model in which to perform genetic screens, but screening assays that are both rapid and can be used to examine a wide variety of cellular and molecular pathways are limited. Drosophila offer an extensive toolbox of GFP-based transcriptional reporters, GFP-tagged proteins, and driver lines which can be used to express GFP in numerous subpopulations of cells. Thus, a tool that can rapidly and quantitatively evaluate GFP levels in Drosophila tissue would provide a broadly applicable screening platform. To quantify GFP levels from Drosophila lysates, we developed a GFP-based ELISA assay. We demonstrate that this assay can detect membrane localized GFP in a variety of neuronal and glial cell populations and validate that it can identify genes that change the morphology of these cells. This assay was also able to detect STAT transcriptional activity after injury. We found that this assay can detect endogenously GFP-tagged proteins, including Draper and Cryptochrome, and it is able to report developmental and circadian changes in the expression of these proteins. Finally, we validated that the assay can be used to detect changes in synapse elimination upon genetic manipulation of astrocytes. We then used the assay to perform a small-scale screen, which identified Syntaxins as novel regulators of astrocyte-mediated synapse elimination. Together, these studies establish an ELISA as a rapid, easy and quantitative in vivo screening method to assay a wide breadth of fundamental questions in neurobiology. Significance StatementForward genetic screens in Drosophila have played an integral role in elucidating the cellular and molecular pathways that govern almost every facet of biology. However, current screening methods in Drosophila are either fast, but limited in their specificity for particular pathways or processes, or rely on imaging, which requires substantial expertise, time, and cost. We have developed a rapid GFP-based ELISA screening method that, when paired with the wealth of GFP-based genetic tools already available in Drosophila, can be used to screen for regulators of many subpopulations of cells, transcriptional programs and levels of thousands of different proteins. Using this assay, we have identified a novel family of genes required for astrocytes to mediate developmental synapse elimination. This technique provides a screening platform that is fast, accessible, and broadly applicable to many pathways and processes, making Drosophila an even more powerful screening tool.

neuroscience↗

bioRxiv2021

Interactions among rooting traits for deep water and nitrogen uptake in upland and lowland ecotypes of switchgrass (Panicum virgatum L.)

Plant phenotypic plasticity in response to nutrient and water availability is an important adaptation for abiotic stress tolerance. Roots intercept water and nutrients while foraging through soil searching for further resources. Substantial amounts of nitrate can leach into groundwater; yet, little is known about how deep rooting affects this process. Here, we phenotyped root system traits and deep 15N nitrate capture across 1.5 m profiles of solid-media using tall mesocosms in switchgrass (Panicum virgatum L.), a cellulosic bioenergy feedstock. Root and shoot biomass, photosynthesis and respiration, and nutrient uptake traits were quantified in response to a water and nitrate stress factorial experiment in the greenhouse for switchgrass upland (VS16) and lowland (AP13) ecotypes. The two switchgrass ecotypes shared common plastic abiotic responses to nitrogen (N) and water availability and yet showed genotypic differences for root and shoot traits. A significant interaction between nitrogen and water stress for axial and lateral root traits represents a complex and shared root development strategy for stress mitigation. Deep root growth and 15N capture were found to be closely linked to aboveground growth. Together, these results represent the wide genetic pool of switchgrass and that deep rooting promotes nitrate capture, plant productivity, and sustainability. HighlightTwo main ecotypes of switchgrass have both shared and different root responses to varying water and nitrogen conditions, with deep rooting shown to be closely linked to aboveground growth.

plant biology↗