Coronaviruses express a papain-like protease (PLpro) that is required for replicase polyprotein maturation and also serves as a deubiquitinating enzyme (DUB). In this study, using a Middle East... Show moreCoronaviruses express a papain-like protease (PLpro) that is required for replicase polyprotein maturation and also serves as a deubiquitinating enzyme (DUB). In this study, using a Middle East respiratory syndrome virus (MERS-CoV) PLpro modified virus in which the DUB is selectively inactivated, we show that the PLpro DUB is an important MERS-CoV interferon antagonist and virulence factor. Although the DUB-negative rMERS-CoVMA replicates robustly in the lungs of human dipeptidyl peptidase 4 knock-in (hDPP4 KI) mice, it does not cause clinical symptoms. Interestingly, a single intranasal vaccination with DUB-negative rMERS-CoVMA induces strong and sustained neutralizing antibody responses and sterilizing immunity after a lethal wt virus challenge. The survival of naive animals also significantly increases when sera from animals vaccinated with the DUB-negative rMERS-CoVMA are passively transferred, prior to receiving a lethal virus dose. These data demonstrate that DUB-negative coronaviruses could be the basis of effective modified live attenuated vaccines.In this work, authors provide a proof-of-concept study showing that deubiquitinating enzyme inactivation in MERS-CoV leads to attenuation in mice, and protection against a lethal challenge. Show less
Although elevated levels of anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA), the in vivo functions of these antibodies remain unclear. Here, we have... Show moreAlthough elevated levels of anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA), the in vivo functions of these antibodies remain unclear. Here, we have expressed monoclonal ACPAs derived from patients with RA, and analyzed their functions in mice, as well as their specificities. None of the ACPAs showed arthritogenicity nor induced pain-associated behavior in mice. However, one of the antibodies, clone E4, protected mice from antibody-induced arthritis. E4 showed a binding pattern restricted to skin, macrophages and dendritic cells in lymphoid tissue, and cartilage derived from mouse and human arthritic joints. Proteomic analysis confirmed that E4 strongly binds to macrophages and certain RA synovial fluid proteins such as alpha-enolase. The protective effect of E4 was epitope-specific and dependent on the interaction between E4-citrullinated alpha-enolase immune complexes with FCGR2B on macrophages, resulting in increased IL-10 secretion and reduced osteoclastogenesis. These findings suggest that a subset of ACPAs have therapeutic potential in RA. Although anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis and generally considered pathogenic, their functional relevance is incompletely understood. In this study, the authors describe an ACPA with a protective effect against antibody-induced arthritis in mice. Show less
Immune cell function can be altered by lipids in circulation, a process potentially relevant to lipid-associated inflammatory diseases including atherosclerosis and rheumatoid arthritis. To gain... Show moreImmune cell function can be altered by lipids in circulation, a process potentially relevant to lipid-associated inflammatory diseases including atherosclerosis and rheumatoid arthritis. To gain further insight in the molecular changes involved, we here perform a transcriptome-wide association analysis of blood triglycerides, HDL cholesterol, and LDL cholesterol in 3229 individuals, followed by a systematic bidirectional Mendelian randomization analysis to assess the direction of effects and control for pleiotropy. Triglycerides are found to induce transcriptional changes in 55 genes and HDL cholesterol in 5 genes. The function and cell-specific expression pattern of these genes implies that triglycerides downregulate both cellular lipid metabolism and, unexpectedly, allergic response. Indeed, a Mendelian randomization approach based on GWAS summary statistics indicates that several of these genes, including interleukin-4 (IL4) and IgE receptors (FCER1A, MS4A2), affect the incidence of allergic diseases. Our findings highlight the interplay between triglycerides and immune cells in allergic disease. Show less
The energy transition will require a rapid deployment of renewable energy (RE) and electric vehicles (EVs) where other transit modes are unavailable. EV batteries could complement RE generation by... Show moreThe energy transition will require a rapid deployment of renewable energy (RE) and electric vehicles (EVs) where other transit modes are unavailable. EV batteries could complement RE generation by providing short-term grid services. However, estimating the market opportunity requires an understanding of many socio-technical parameters and constraints. We quantify the global EV battery capacity available for grid storage using an integrated model incorporating future EV battery deployment, battery degradation, and market participation. We include both in-use and end-of-vehicle-life use phases and find a technical capacity of 32–62 terawatt-hours by 2050. Low participation rates of 12%–43% are needed to provide short-term grid storage demand globally. Participation rates fall below 10% if half of EV batteries at end-of-vehicle-life are used as stationary storage. Short-term grid storage demand could be met as early as 2030 across most regions. Our estimates are generally conservative and offer a lower bound of future opportunities. Show less
Lei, X.; Khatri, I.; Wit, T. de; Rink, I. de; Nieuwland, M.; Kerkhoven, R.; ... ; Xiao, Y.L. 2023
Despite their low abundance in the tumor microenvironment (TME), classical type 1 dendritic cells (cDC1) play a pivotal role in anti-cancer immunity, and their abundance positively correlates with... Show moreDespite their low abundance in the tumor microenvironment (TME), classical type 1 dendritic cells (cDC1) play a pivotal role in anti-cancer immunity, and their abundance positively correlates with patient survival. However, their interaction with CD4(+) T-cells to potentially enable the cytotoxic T lymphocyte (CTL) response has not been elucidated. Here we show that contact with activated CD4(+) T-cells enables human ex vivo cDC1, but no other DC types, to induce a CTL response to cell-associated tumor antigens. Single cell transcriptomics reveals that CD4(+) T-cell help uniquely optimizes cDC1 in many functions that support antigen cross-presentation and T-cell priming, while these changes don't apply to other DC types. We robustly identify "helped" cDC1 in the TME of a multitude of human cancer types by the overlap in their transcriptomic signature with that of recently defined, tumor-infiltrating DC states that prove to be positively prognostic. As predicted from the functional effects of CD4(+) T-cell help, the transcriptomic signature of "helped" cDC1 correlates with tumor infiltration by CTLs and Thelper(h)-1 cells, overall survival and response to PD-1-targeting immunotherapy. These findings reveal a critical role for CD4(+) T-cell help in enabling cDC1 function in the TME and may establish the helped cDC1 transcriptomic signature as diagnostic marker in cancer.The presence of classical type 1 dendritic cells (cDC1) positively influences prognosis in cancer, but their intricate networking with the various T cell types found in the tumour microenvironment is not fully appreciated. Here the authors show that cDC1 encounter with CD4(+) helper T-cells transforms their gene expression signature, and these "helped" dendritic cells enable the function of anti-tumour cytotoxic T-cells. Show less
Synthase-dependent secretion systems are a conserved mechanism for producing exopolysaccharides in Gram-negative bacteria. Although widely studied, it is not well understood how these systems are... Show moreSynthase-dependent secretion systems are a conserved mechanism for producing exopolysaccharides in Gram-negative bacteria. Although widely studied, it is not well understood how these systems are organized to coordinate polymer biosynthesis, modification, and export across both membranes and the peptidoglycan. To investigate how synthase-dependent secretion systems produce polymer at a molecular level, we determined the crystal structure of the AlgK-AlgX (AlgKX) complex involved in Pseudomonas aeruginosa alginate exopolysaccharide acetylation and export. We demonstrate that AlgKX directly binds alginate oligosaccharides and that formation of the complex is vital for polymer production and biofilm attachment. Finally, we propose a structural model for the AlgEKX outer membrane modification and secretion complex. Together, our study provides insight into how alginate biosynthesis proteins coordinate production of a key exopolysaccharide involved in establishing persistent Pseudomonas lung infections. Show less
Sister chromatid exchanges (SCEs) are considered to be products of homologous recombination repair. The authors show that SCEs can arise independently of homologous recombination due to processing... Show moreSister chromatid exchanges (SCEs) are considered to be products of homologous recombination repair. The authors show that SCEs can arise independently of homologous recombination due to processing of replication intermediates during mitosis.Sister chromatid exchanges (SCEs) are products of joint DNA molecule resolution, and are considered to form through homologous recombination (HR). Indeed, SCE induction upon irradiation requires the canonical HR factors BRCA1, BRCA2 and RAD51. In contrast, replication-blocking agents, including PARP inhibitors, induce SCEs independently of BRCA1, BRCA2 and RAD51. PARP inhibitor-induced SCEs are enriched at difficult-to-replicate genomic regions, including common fragile sites (CFSs). PARP inhibitor-induced replication lesions are transmitted into mitosis, suggesting that SCEs can originate from mitotic processing of under-replicated DNA. Proteomics analysis reveals mitotic recruitment of DNA polymerase theta (POLQ) to synthetic DNA ends. POLQ inactivation results in reduced SCE numbers and severe chromosome fragmentation upon PARP inhibition in HR-deficient cells. Accordingly, analysis of CFSs in cancer genomes reveals frequent allelic deletions, flanked by signatures of POLQ-mediated repair. Combined, we show PARP inhibition generates under-replicated DNA, which is processed into SCEs during mitosis, independently of canonical HR factors. Show less
Membrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or... Show moreMembrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or metabolic adaptation. PML NBs recruit many partner proteins, but the actual biochemical mechanism underlying their pleiotropic functions remains elusive. Similarly, PML role in embryonic stem cell (ESC) and retro-element biology is unsettled. Here we demonstrate that PML is essential for oxidative stress-driven partner SUMO2/3 conjugation in mouse ESCs (mESCs) or leukemia, a process often followed by their poly-ubiquitination and degradation. Functionally, PML is required for stress responses in mESCs. Differential proteomics unravel the KAP1 complex as a PML NB-dependent SUMO2-target in arsenic-treated APL mice or mESCs. PML-driven KAP1 sumoylation enables activation of this key epigenetic repressor implicated in retro-element silencing. Accordingly, Pml−/− mESCs re-express transposable elements and display 2-Cell-Like features, the latter enforced by PML-controlled SUMO2-conjugation of DPPA2. Thus, PML orchestrates mESC state by coordinating SUMO2-conjugation of different transcriptional regulators, raising new hypotheses about PML roles in cancer. Show less
Kapteijn, R.; Shitut, S.S.; Aschmann, D.; Zhang, L.; Beer, M. de; Daviran, D.; ... ; Claessen, D. 2022
Horizontal gene transfer in bacteria can occur through mechanisms such as conjugation, transduction and transformation, which facilitate the passage of DNA across the cell wall. Here, Kapteijn et... Show moreHorizontal gene transfer in bacteria can occur through mechanisms such as conjugation, transduction and transformation, which facilitate the passage of DNA across the cell wall. Here, Kapteijn et al. show that cell wall-deficient bacteria can take up DNA and other extracellular materials via an endocytosis-like process.Horizontal gene transfer in bacteria is widely believed to occur via conjugation, transduction and transformation. These mechanisms facilitate the passage of DNA across the protective cell wall using sophisticated machinery. Here, we report that cell wall-deficient bacteria can engulf DNA and other extracellular material via an endocytosis-like process. Specifically, we show that L-forms of the filamentous actinomycete Kitasatospora viridifaciens can take up plasmid DNA, polysaccharides (dextran) and 150-nm lipid nanoparticles. The process involves invagination of the cytoplasmic membrane, leading to formation of intracellular vesicles that encapsulate extracellular material. DNA uptake is not affected by deletion of genes homologous to comEC and comEA, which are required for natural transformation in other species. However, uptake is inhibited by sodium azide or incubation at 4 degrees C, suggesting the process is energy-dependent. The encapsulated materials are released into the cytoplasm upon degradation of the vesicle membrane. Given that cell wall-deficient bacteria are considered a model for early life forms, our work reveals a possible mechanism for primordial cells to acquire food or genetic material before invention of the bacterial cell wall. Show less
Peeters, R.; Cuenca-Escalona, J.; Zaal, E.A.; Hoekstra, A.T.; Balvert, A.C.G.; Vidal-Manrique, M.; ... ; Spriel, A.B. van 2022
The importance of fatty acid (FA) metabolism in cancer is well-established, yet the mechanisms underlying metabolic reprogramming remain elusive. Here, we identify tetraspanin CD37, a prognostic... Show moreThe importance of fatty acid (FA) metabolism in cancer is well-established, yet the mechanisms underlying metabolic reprogramming remain elusive. Here, we identify tetraspanin CD37, a prognostic marker for aggressive B-cell lymphoma, as essential membrane-localized inhibitor of FA metabolism. Deletion of CD37 on lymphoma cells results in increased FA oxidation shown by functional assays and metabolomics. Furthermore, CD37-negative lymphomas selectively deplete palmitate from serum in mouse studies. Mechanistically, CD37 inhibits the FA transporter FATP1 through molecular interaction. Consequently, deletion of CD37 induces uptake and processing of exogenous palmitate into energy and essential building blocks for proliferation, and inhibition of FATP1 reverses this phenotype. Large lipid deposits and intracellular lipid droplets are observed in CD37-negative lymphoma tissues of patients. Moreover, inhibition of carnitine palmitoyl transferase 1 A significantly compromises viability and proliferation of CD37-deficient lymphomas. Collectively, our results identify CD37 as a direct gatekeeper of the FA metabolic switch in aggressive B-cell lymphoma.Tetraspanin CD37 deficiency has been reported as a prognostic marker for aggressive B-cell lymphoma. Here, the authors show that CD37 interacts with the fatty acid transporter 1 to inhibit palmitate uptake and its deficiency leads to increased fatty acid metabolism which promotes tumorigenesis in B-cell lymphoma. Show less
Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded... Show moreExercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n = 31, and VIG-EX; n = 31). We observed no changes in BAT volume (Delta Control: -22.2 +/- 52.6 ml; Delta MOD-EX: -15.5 +/- 62.1 ml, Delta VIG-EX: -6.8 +/- 66.4 ml; P = 0.771) or F-18-fluorodeoxyglucose uptake (SUVpeak Delta Control: -2.6 +/- 3.1 ml; Delta MOD-EX: -1.2 +/- 4.8, Delta VIG-EX: -2.2 +/- 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.Exercise modulates brown adipose tissue (BAT) metabolism in murine models. Here the authors report that there is no evidence that 24 weeks of supervised exercise training modulates BAT volume or function in young sedentary adults in the ACTIBATE randomized controlled trial. Show less
Kooij, B. van de; Kruswick, A.; Attikum, H. van; Yaffe, M.B. 2022
DNA double-strand breaks (DSB) are repaired by multiple distinct pathways, with outcomes ranging from error-free repair to mutagenesis and genomic loss. DSB-repair pathway cross-talk and... Show moreDNA double-strand breaks (DSB) are repaired by multiple distinct pathways, with outcomes ranging from error-free repair to mutagenesis and genomic loss. DSB-repair pathway cross-talk and compensation is incompletely understood, despite its importance for genomic stability, oncogenesis, and genome editing using CRISPR/Cas9. To address this, we constructed and validated three fluorescent Cas9-based reporters, named DSB-Spectrum, that simultaneously quantify the contribution of multiple DNA repair pathways at a DSB. DSB-Spectrum reporters distinguish between DSB-repair by error-free canonical non-homologous end-joining (c-NHEJ) versus homologous recombination (HR; reporter 1), mutagenic repair versus HR (reporter 2), and mutagenic end-joining versus single strand annealing (SSA) versus HR (reporter 3). Using these reporters, we show that inhibiting the c-NHEJ factor DNA-PKcs increases repair by HR, but also substantially increases mutagenic SSA. Our data indicate that SSA-mediated DSB-repair also occurs at endogenous genomic loci, driven by Alu elements or homologous gene regions. Finally, we demonstrate that long-range end-resection factors DNA2 and Exo1 promote SSA and reduce HR, when both pathways compete for the same substrate. These new Cas9-based DSB-Spectrum reporters facilitate the comprehensive analysis of repair pathway crosstalk and DSB-repair outcome.Correct repair of broken DNA molecules is required to prevent potentially oncogenic mutations. To study repair fidelity and mechanism, van de Kooij et al. developed single cell reporters that detect if DNA breaks are fixed by error-free or mutagenic repair. Show less
Sabatini, F.M.; Jiménez-Alfaro, B.; Jandt, U.; Chytrý, M.; Field, R.; Kessler, M.; ... ; Bruelheide, H. 2022
Global patterns of regional (gamma) plant diversity are relatively well known, but whether these patterns hold for local communities, and the dependence on spatial grain, remain controversial.... Show moreGlobal patterns of regional (gamma) plant diversity are relatively well known, but whether these patterns hold for local communities, and the dependence on spatial grain, remain controversial. Using data on 170,272 georeferenced local plant assemblages, we created global maps of alpha diversity (local species richness) for vascular plants at three different spatial grains, for forests and non-forests. We show that alpha diversity is consistently high across grains in some regions (for example, Andean-Amazonian foothills), but regional ‘scaling anomalies’ (deviations from the positive correlation) exist elsewhere, particularly in Eurasian temperate forests with disproportionally higher fine-grained richness and many African tropical forests with disproportionally higher coarse-grained richness. The influence of different climatic, topographic and biogeographical variables on alpha diversity also varies across grains. Our multi-grain maps return a nuanced understanding of vascular plant biodiversity patterns that complements classic maps of biodiversity hotspots and will improve predictions of global change effects on biodiversity. Show less
Blessing, C.; Apelt, K.; Heuvel, D. van den; Gonzalez-Leal, C.; Rother, M.B.; Woude, M. van der; ... ; Luijsterburg, M.S. 2022
Cells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of... Show moreCells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown. Here, we identify the poly-(ADP-ribose) polymerases PARP1 and PARP2 as constitutive interactors of XPC. Their interaction results in the XPC-stimulated synthesis of poly-(ADP-ribose) (PAR) by PARP1 at UV lesions, which in turn enables the recruitment and activation of the PAR-regulated chromatin remodeler ALC1. PARP2, on the other hand, modulates the retention of ALC1 at DNA damage sites. Notably, ALC1 mediates chromatin expansion at UV-induced DNA lesions, leading to the timely clearing of CPD lesions. Thus, we reveal how chromatin containing difficult-to-repair DNA lesions is primed for repair, providing insight into mechanisms of chromatin plasticity during GGR.Cells employ global genome nucleotide excision repair to repair a broad spectrum of genomic DNA lesions. Here, the authors reveal how chromatin is primed for repair, providing insight into mechanisms of chromatin plasticity during DNA repair. Show less
Xie, F.; Zhou, X.X.; Su, P.; Li, H.Y.; Tu, Y.F.; J.J. du; ... ; Zhou, F.F. 2022
Understanding the factors that hamper immune therapy in breast cancer may increase the range of patients who benefit. Here authors show that breast cancer cells produce and subsequently transfer... Show moreUnderstanding the factors that hamper immune therapy in breast cancer may increase the range of patients who benefit. Here authors show that breast cancer cells produce and subsequently transfer active TGF-beta type II receptors to CD8 + T cells to render them exhausted, thus paralyzing the anti-tumor immune response.Cancer immunotherapies have shown clinical success in various types of tumors but the patient response rate is low, particularly in breast cancer. Here we report that malignant breast cancer cells can transfer active TGF-beta type II receptor (T beta RII) via tumor-derived extracellular vesicles (TEV) and thereby stimulate TGF-beta signaling in recipient cells. Up-take of extracellular vesicle-T beta RII (EV-T beta RII) in low-grade tumor cells initiates epithelial-to-mesenchymal transition (EMT), thus reinforcing cancer stemness and increasing metastasis in intracardial xenograft and orthotopic transplantation models. EV-T beta RII delivered as cargo to CD8(+) T cells induces the activation of SMAD3 which we demonstrated to associate and cooperate with TCF1 transcription factor to impose CD8(+) T cell exhaustion, resulting in failure of immunotherapy. The levels of T beta RII+ circulating extracellular vesicles (crEV) appears to correlate with tumor burden, metastasis and patient survival, thereby serve as a non-invasive screening tool to detect malignant breast tumor stages. Thus, our findings not only identify a possible mechanism by which breast cancer cells can promote T cell exhaustion and dampen host anti-tumor immunity, but may also identify a target for immune therapy against the most devastating breast tumors. Show less
Pardieck, I.N.; Sluis, T.C. van der; Gracht, E.T.I. van der; Veerkamp, D.M.B.; Behr, F.M.; Duikeren, S. van; ... ; Arens, R. 2022
Vaccination regimens and the number of doses required for optimal immunity and protection are critical factors in the translation of vaccines. Here the authors show administration of a three dose... Show moreVaccination regimens and the number of doses required for optimal immunity and protection are critical factors in the translation of vaccines. Here the authors show administration of a three dose protocol of a single T cell epitope to the SARS-CoV-2 spike protein induces a robust CD8(+) T cell response and confers protection in a lethal murine challenge model of infection.Understanding the mechanisms and impact of booster vaccinations are essential in the design and delivery of vaccination programs. Here we show that a three dose regimen of a synthetic peptide vaccine elicits an accruing CD8(+) T cell response against one SARS-CoV-2 Spike epitope. We see protection against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, but two dose approaches are insufficient to confer protection. The third vaccine dose of the single T cell epitope peptide results in superior generation of effector-memory T cells and tissue-resident memory T cells, and these tertiary vaccine-specific CD8(+) T cells are characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping shows that a substantial fraction of the tertiary CD8(+) effector-memory T cells develop from re-migrated tissue-resident memory T cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8(+) T cell response leading to protection against otherwise lethal SARS-CoV-2 infection. Show less
Lombardo, U.; Arroyo-Kalin, M.; Schmidt, M.; Huisman, H.; Lima, H.P.; de Paula Moraes, C.; ... ; Teixeira, W.G. 2022
Microbiomes play a pivotal role in plant growth and health, but the genetic factors involved in microbiome assembly remain largely elusive. Here, we map the molecular features of the rhizosphere... Show moreMicrobiomes play a pivotal role in plant growth and health, but the genetic factors involved in microbiome assembly remain largely elusive. Here, we map the molecular features of the rhizosphere microbiome as quantitative traits of a diverse hybrid population of wild and domesticated tomato. Gene content analysis of prioritized tomato quantitative trait loci suggests a genetic basis for differential recruitment of various rhizobacterial lineages, including a Streptomyces-associated 6.31 Mbp region harboring tomato domestication sweeps and encoding, among others, the iron regulator FIT and the water channel aquaporin SlTIP2.3. Within metagenome-assembled genomes of root-associated Streptomyces and Cellvibrio, we identify bacterial genes involved in metabolism of plant polysaccharides, iron, sulfur, trehalose, and vitamins, whose genetic variation associates with specific tomato QTLs. By integrating ‘microbiomics’ and quantitative plant genetics, we pinpoint putative plant and reciprocal rhizobacterial traits underlying microbiome assembly, thereby providing a first step towards plant-microbiome breeding programs. Show less
