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Luo, E.

Publications and source records attributed to Luo, E..

13 recordsLinked to original sources

The cellular and genetic basis of inflorescence divergence between maize and teosinte

The domestication of maize from teosinte involved dramatic remodeling of the ear, yet the cellular and genetic bases of this transformation remain unclear. Here, we generate a single-nucleus and spatial transcriptome atlas of developing maize and teosinte ears. Comparative analysis reveals divergence in cob-associated cell types, with enhanced cytokinin signaling and reduced growth-inhibitory signals collectively driving cob thickening and enlargement in maize. We further demonstrate that domestication expanded the spatial expression domain of key transcription factors in maize meristem cells, enhancing the potential for increasing kernel number. Additionally, we verified a major domestication gene, ZmSPD1, in which two nonsynonymous SNPs differentiate maize from teosinte and alter jasmonic acid (JA) levels in the ear, thereby suppressing spikelet abortion to effectively double kernel production. These findings provide a cell-resolved mechanistic framework for how cob architecture and kernel number were shaped during maize domestication, offering new insights into the formation of key agronomic traits.

plant biology↗

The biogeography of hydrothermal vent giant viruses across the global ocean

Viruses are the most abundant known biological entities in the ocean and play central role in microbial ecology. However, the patterns and drivers of their biogeographic distribution across global ocean remain poorly understood. Here, we conducted large-scale metagenomic analysis of 514 samples from globally-distributed hydrothermal vents and the pelagic ocean to examine the biogeography of giant viruses, a widespread viral group in the ocean. We identified 279 putative giant virus populations from hydrothermal vents and 56 populations were broadly distributed across hydrothermal vents. Vent-derived giant viruses are also present in the global pelagic ocean showing an "everything is everywhere" biogeographic pattern. We identified the mechanistic processes governing this global distribution of giant viruses and found that horizontal passive transport, mediated by hydrothermal plumes, is likely a major mechanism that drives the global connectivity of vent-derived giant viruses. Additionally, environmental selection appears to shape viral distributions within high-temperature vent habitats, as giant viruses encoding heat-shock proteins were enriched in these environments. Overall, this study identified the key process that sustain global-scale ecological connectivity for viruses between hydrothermal vents and pelagic ocean and demonstrates that a classic microbial biogeography paradigm, "everything is everywhere, but the environment selects" applies to marine giant viruses.

ecology↗

Alternative polyadenylation drives isoform-dependent m6A remodeling during Zika virus infection

Alternative RNA processing generates extensive transcript diversity, yet how transcript architecture influences selective m6A deposition is incompletely understood. Exon-junction-based models explain where m6A is excluded, but a positive determinant of m6A accumulation remains undefined. Here, we leverage Zika virus-induced changes in m6A deposition to uncover determinants of transcript-selective methylation. By integrating GLORI-seq, native METTL3 RNA immunoprecipitation, and nanopore direct RNA sequencing, we generate a single-nucleotide, isoform-resolved map of m6A dynamics during infection. We identify over 2,000 dynamic m6A sites, many arising from changes in transcript architecture, and pinpoint proximal polyadenylation sites as positive determinants of m6A accumulation. The cleavage stimulation factors CSTF2 and CSTF2T drive this remodeling through two routes: redundant induction of intronic polyadenylation, which converts internal exons into terminal exons that expose DRACH motifs to METTL3, and non-redundant, cleavage-independent recruitment of METTL3 near proximal polyadenylation sites, establishing alternative polyadenylation as a key architectural determinant of the m6A landscape.

molecular biology↗

Autoregressive forecasting of future single-cell state transitions

Predicting future cell state transitions from static transcriptomic snapshots is vital for understanding and steering cellular dynamics. Although existing trajectory and RNA velocity methods can infer local transitions within observed data, they are fundamentally limited in extrapolating long-range cellular dynamics. Here, we introduce CellTempo, an autoregressive generative framework that enables long-range forecasting of cell state trajectories directly from static transcriptomic snapshots. CellTempo is pretrained on scBaseTraj, a large-scale collection of multi-step cellular transition sequences constructed by integrating diverse experimental technologies and data sources. Across diverse biological systems, CellTempo accurately predicts long-range lineage progression and reconstructs unseen cellular potential landscapes. It further distinguishes transient perturbation responses from long-term cell-fate changes, enabling prioritization of candidate compounds for cell-fate engineering. These results demonstrate that long-range cellular dynamics are inferable from static observations, establishing a foundation for predictive and controllable modeling of cell fate.

bioinformatics↗

Virus-mediated recycling of chemoautotrophic biomass

Aquatic environments absorb [~]2.5 gigatonnes of atmospheric carbon each year1, more than the carbon stored in the atmosphere, soils, and all biomass combined. Primary producers transform this dissolved inorganic carbon into biomass that can subsequently flow into other trophic levels, or be released back into the environment through viral lysis. While there is substantial knowledge about the diversity and activity of viruses infecting photoautotrophic primary producers, little is known about viruses infecting chemoautotrophs, representing a gap in our understanding of key microbial processes driving global carbon cycles. Here, we combine metagenomics with 12/13C stable isotopic probing mesocosm experiments in a marine-derived meromictic pond to quantify lineage-specific carbon cycling activity to identify key microbial populations driving carbon cycling. We then tracked the flow of carbon from active chemoautotrophs to their viruses and found evidence supporting virus-mediated recycling of chemoautotrophic biomass through the production of viral particles. In particular, active populations of hydrogen/sulfur-oxidizing chemoautotrophs (Thiomicrorhabdus, Hydrogenovibrio, Sulfurimonas, Sulfurovum) were targeted by viruses. Considering the widespread distribution of chemoautotrophs on Earth, we postulate that this previously overlooked component of the microbial carbon cycle is a globally relevant process that has implications for our planets carbon cycle. This work provides the foundation for revealing the role of viral lysis in chemoautotrophic primary production and builds toward biogeochemical models that incorporate viral recycling of chemoautotrophic biomass. Summary statementThe diversity, mechanisms, and processes governing microbial primary production and the recycling of autotrophic biomass are fundamental to our planets carbon cycle. These processes have implications for carbon sequestration, ocean biogeochemistry, and the overall balance of carbon dioxide in the atmosphere. Beneath the Earths sunlit layer, primary production is driven by microbial chemoautotrophs that derive energy from the oxidation of reduced compounds, such as hydrogen and sulfur, to form the base of the food web. Growing evidence suggests that aquatic ecosystems fueled by chemoautotrophy are widely distributed on Earth, ranging from beneath ice shelves to coastal upwelling regions to oxygen minimum zones, deep-sea hydrothermal vents and cold seeps, groundwater, and meromictic ponds and lakes2-7. Studying microbial processes regulating chemoautotrophic primary production and the recycling of chemoautotrophic biomass is fundamental to our understanding of global carbon cycles. While the diversity, function, and activity of viruses targeting photoautotrophs have been well-described across aquatic ecosystems8, we have little understanding of viruses involved in the recycling of chemoautotrophic biomass. Viruses are a major source of cellular mortality and carbon cycling in aquatic environments9-11. Viral lysis is estimated to transform [~]150 gigatonnes of carbon annually from biomass back into the environment, equivalent to [~]25 times that of the oceans biological carbon pump12,13. Despite recognition of the important role of viruses in aquatic habitats, there is a large gap in our understanding of the impact of viruses on globally distributed chemoautotrophs2,4,5,14-18. In this study, we show that viruses are not merely passive players but active agents recycling carbon fixed by productive chemoautotrophs, fundamentally reshaping how we view carbon and nutrient cycling in redox-active ecosystems.

microbiology↗

Multi-modal Diffusion Model with Dual-Cross-Attention for Multi-Omics Data Generation and Translation

Single-cell multi-omics technologies offer unprecedented opportunities to decipher complex cellular mechanisms. To overcome experimental limitations in scale, cost, and coverage, powerful computational methods are essential for integrating diverse data modalities and generating high-fidelity in-silico data. In this paper, we present scDiffusion-X, a latent diffusion model specifically designed for this purpose. The core innovation is a Dual-Cross-Attention (DCA) module that adaptively learns intricate, hidden relationships between different molecular modalities, offering a more flexible and interpretable approach than traditional integration strategies. Extensive benchmarking experiments demonstrate that scDiffusion-X excels at generating realistic multi-omics data, preserving cellular heterogeneity and global data structures with excellent scalability. Distinct from existing multi-omics simulators, scDiffusion-X uniquely enables high-fidelity modality translation by predicting one molecular modality from another and provides robust uncertainty quantification. Beyond data generation, we designed a gradient-based interpretation framework to transform DCA module into a discovery tool, enabling inference of comprehensive cell-type-specific heterogeneous gene regulatory networks (GRNs). By integrating state-of-the-art generative modeling with deep biological interpretability, scDiffusion-X serves as a powerful tool for dissecting regulatory relationships, predicting perturbation responses, poised to accelerate discovery in single-cell multi-omics research.

bioinformatics↗

Characterization and genomic analysis of the Lyme disease spirochete bacteriophage phiBB-1

Lyme disease is a tick-borne infection caused by the spirochete Borrelia (Borreliella) burgdorferi. Borrelia species have highly fragmented genomes composed of a linear chromosome and a constellation of linear and circular plasmids some of which are required throughout the enzootic cycle. Included in this plasmid repertoire by almost all Lyme disease spirochetes are the 32-kb circular plasmid cp32 prophages that are capable of lytic replication to produce infectious virions called {phi}BB-1. While the B. burgdorferi genome contains evidence of horizontal transfer, the mechanisms of gene transfer between strains remain unclear. While we know that {phi}BB-1 transduces cp32 and shuttle vector DNA during in vitro cultivation, the extent of {phi}BB-1 DNA transfer is not clear. Herein, we use proteomics and long-read sequencing to further characterize {phi}BB-1 virions. Our studies identified the cp32 pac region and revealed that {phi}BB-1 packages linear cp32s via a headful mechanism with preferentially packaging of plasmids containing the cp32 pac region. Additionally, we find {phi}BB-1 packages fragments of the linear chromosome and full-length plasmids including lp54, cp26, and others. Furthermore, sequencing of {phi}BB-1 packaged DNA allowed us to resolve the covalently closed hairpin telomeres for the linear B. burgdorferi chromosome and most linear plasmids in strain CA-11.2A. Collectively, our results shed light on the biology of the ubiquitous {phi}BB-1 phage and further implicates {phi}BB-1 in the generalized transduction of diverse genes and the maintenance of genetic diversity in Lyme disease spirochetes.

microbiology↗

Marine viral particles reveal an expansive repertoire of phage-parasitizing mobile elements

Phage satellites are mobile genetic elements that propagate by parasitizing bacteriophage replication. We report here the discovery of abundant and diverse phage satellites that were packaged as concatemeric repeats within naturally occurring bacteriophage particles in seawater. These same phage-parasitizing mobile elements were found integrated in the genomes of dominant co-occurring bacterioplankton species. Like known phage satellites, many of the marine phage satellites encoded genes for integration, DNA replication, phage interference, and capsid assembly. Many also contained distinctive gene suites indicative of unique virus hijacking, phage interference and mobilization mechanisms. Marine phage satellite sequences were widespread in local and global oceanic virioplankton populations, reflecting their ubiquity, abundance, and temporal persistence in marine planktonic communities worldwide. Their gene content and putative life cycles suggest they may impact host-cell phage immunity and defense, lateral gene transfer, and bacteriophage-induced cell mortality and host and virus productivity. These previously unrecognized marine phage satellites therefore have potential to impact the ecology and evolution of bacteria and their bacteriophages in the ocean, and similar phage parasites likely thrive in many other microbial habitats as well. Significance statementPhage satellites are mobile genetic elements that parasitize bacteriophage, thereby exerting profound biological and ecological impacts. To date however, phage satellites have been found primarily in Gram-positive cocci and a few Gram-negative bacteria, many of which are human pathogens. Direct inspection of "wild" marine virus particles however, revealed that phage satellites are widely distributed in the sea, and that their genetic diversity, gene repertoires, and host ranges are much greater than previously supposed. Our analyses provide insight into their parasitic life cycles, potential satellite-helper-phage interactions, and reproductive strategies of these newly recognized phage-parasitizing mobile elements. Their properties, diversity and environmental distributions suggest they exert pervasive influence on marine plankton ecology and bacterial and virus evolution in the sea.

microbiology↗

proovframe: frameshift-correction for long-read (meta)genomics

Long-read sequencing technologies hold big promises for the genomic analysis of complex samples such as microbial communities. Yet, despite improving accuracy, basic gene prediction on long-read data is still often impaired by frameshifts resulting from small indels. Consensus polishing using either complementary short reads or to a lesser extent the long reads themselves can mitigate this effect but requires universally high sequencing depth, which is difficult to achieve in complex samples where the majority of community members are rare. Here we present proovframe, a software implementing an alternative approach to overcome frameshift errors in long-read assemblies and raw long reads. We utilize protein-to-nucleotide alignments against reference databases to pinpoint indels in contigs or reads and correct them by deleting or inserting 1-2 bases, thereby conservatively restoring reading-frame fidelity in aligned regions. Using simulated and real-world benchmark data we show that proovframe performs comparably to short-read-based polishing on assembled data, works well with remote protein homologs, and can even be applied to raw reads directly. Together, our results demonstrate that protein-guided frameshift correction significantly improves the analyzability of long-read data both in combination with and as an alternative to common polishing strategies. Proovframe is available from https://github.com/thackl/proovframe.

bioinformatics↗

Novel integrative elements and genomic plasticity in ocean ecosystems

Horizontal gene transfer accelerates microbial evolution, promoting diversification and adaptation. The globally abundant marine cyanobacterium Prochlorococcus has a highly streamlined genome with frequent gene exchange reflected in its extensive pangenome. The source of its genomic variability, however, remains elusive since most cells lack the common mechanisms that enable horizontal gene transfer, including conjugation, transformation, plasmids and prophages. Examining 623 genomes, we reveal a diverse system of mobile genetic elements - cargo-carrying transposons we named tycheposons - that shape Prochlorococcus genomic plasticity. The excision and integration of tycheposons at seven tRNA genes drive the remodeling of larger genomic islands containing most of Prochlorococcus flexible genes. Most tycheposons carry genes important for niche differentiation through nutrient acquisition; others appear similar to phage parasites. Tycheposons are highly enriched in extracellular vesicles and phage particles in ocean samples, suggesting efficient routes for their dispersal, transmission and propagation. Supported by evidence for similar elements in other marine microbes, our work underpins the role of vesicle- and virus-mediated transfer of mobile genetic elements in the diversification and adaptation of microbes in dilute aquatic environments - adding a significant piece to the puzzle of what governs microbial evolution in the planets largest habitat.

microbiology↗

Pyruvate Kinase M Links Glucose Availability to Protein Synthesis

How human cells coordinate various metabolic processes, such as glycolysis and protein translation, remains unclear. One key insight is that various metabolic enzymes have been found to associate with mRNAs, however whether these enzymes regulate mRNA biology in response to changes in cellular metabolic state remains unknown. Here we report that the glycolytic enzyme, pyruvate kinase M (PKM), inhibits the translation of 7% of the transcriptome in response to elevated levels of glucose and pyruvate. Our data suggest that in the presence of glucose and pyruvate, PKM associates with ribosomes that are synthesizing stretches of polyacidic nascent polypeptides and stalls the elongation step of translation. PKM-regulated mRNAs encode proteins required for the cell cycle and may explain previous results linking PKM to cell cycle regulation. Our study uncovers an unappreciated link between glycolysis and the ribosome that likely coordinates the intake of glycolytic metabolites with the regulation of protein synthesis and the cell cycle.

molecular biology↗

Assembly-free single-molecule nanopore sequencing recovers complete virus genomes from natural microbial communities

Viruses are the most abundant biological entities on Earth, and play key roles in host ecology, evolution, and horizontal gene transfer. Despite recent progress in viral metagenomics, the inherent genetic complexity of virus populations still poses technical difficulties for recovering complete virus genomes from natural assemblages. To address these challenges, we developed an assembly-free, single-molecule nanopore sequencing approach enabling direct recovery of high-quality viral genome sequences from environmental samples. Our method yielded over a thousand high quality, full-length draft virus genome sequences that could not be fully recovered using short read assembly approaches applied to the same samples. Additionally, novel DNA sequences were discovered whose repeat structures, gene contents and concatemer lengths suggested that they represent phage-inducible chromosomal islands that were packaged as concatemers within phage particles. Our new approach provided novel insight into genome structures, population biology, and ecology of naturally occurring viruses and viral parasites.

microbiology↗

Proximity labeling reveals an extensive steady-state stress granule interactome and insights to neurodegeneration

Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form in response to proteotoxic stress. Although SGs are distinct from aggregates observed in neurodegenerative disorders, they share protein components. We used APEX-mediated proximity labeling combined with quantitative mass spectrometry and high-throughput imaging to identify >100 previously unknown SG proteins in human cells, about 10% of which localize to SGs in a cell type- or stress type-dependent manner. Supporting a link between SG proteins and neurodegeneration, we demonstrate aberrant SG composition and subcellular distribution in iPSC-derived motor neurons from ALS patients, and identify several known and previously unidentified SG proteins that modify toxicity of mutant FUS and TDP-43 overexpression in Drosophila. We show that even in an unstressed steady-state, SG proteins form a densely-connected protein interaction network (PIN) and propose a model in which existing RNPs coalesce rapidly into microscopically visible granules that can act as gateways to pathological protein aggregation.\n\nHighlights O_LIAPEX proximity labeling of dynamic RNP granules identifies over 100 novel SG proteins\nC_LIO_LISG proteins form a densely-connected protein interaction network in unstressed cells\nC_LIO_LISystematic immunofluorescence analysis reveals stress- and cell type-specific SG composition\nC_LIO_LIALS motor neurons contain SGs with distinct content and subcellular distribution\nC_LI

cell biology↗