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Yi, E.

Publications and source records attributed to Yi, E..

9 recordsLinked to original sources
bioRxiv2026

Strong effects of soil microbes on early-life defense alter phenotypic correlations in plant leaves

Microbes have wide-ranging effects on host phenotype. However, whether these effects extend to the relationships among host traits remains unknown. We tested whether microbes affect phenotypic correlations among early life traits in the weedy legume Medicago lupulina. In a field common garden, we inoculated plants with two types of microbes: nitrogen-fixing bacteria and rhizosphere microbial communities. We found that microbes modify phenotypic integration (phenotypic correlations) in leaves, primarily due to effects on independent effects on leaflet area and trichome density, a defense trait. While microbial effects on leaflet size were associated with overall plant growth, variation in trichome density was decoupled from growth and not predicted by investment in mutualism. Our results highlight the unique insights that can come from a multivariate approach to organismal plasticity, and raise the intriguing possibility that microbes may have an outsized impact on defense traits and their integration with organismal function.

Plant Biology↗
bioRxiv2025

Selective depletion of cancer cells with extrachromosomal DNA via lentiviral infection

Dear Editor Extrachromosomal DNA (ecDNA), a major focal oncogene amplification mode found across cancer, has recently regained attention as an emerging cancer hallmark1,2, with a pervasive presence across cancers3,4. With technical advancements such as high-coverage sequencing and live-cell genome imaging, we can now investigate ecDNAs behaviors and functions 5-7. However, we still lack an understanding of how to eliminate ecDNA. We observed depletion of cells containing ecDNA during lentiviral but not transposon-based transduction while we sought to investigate the mechanism of ecDNA behavior. This discovery may provide critical information on utilizing a lentiviral system in emerging ecDNA research. Additionally, this observation suggests specific sensitivities for cells with ecDNA.

cancer biology↗
bioRxiv2024

Variation in a microbial mutualist has cascading consequences for host-parasite interactions

Strains of microbial symbionts often vary in their effect on their host. However, little is known about how the genetic variation in microbial symbiont populations impacts host interactions with other co-colonizing microbes. We investigated how different strains of nitrogen-fixing rhizobial bacteria affect their host plants response to parasitic root-knot nematodes in the legume Medicago truncatula. Using dual RNAseq of the root organs harboring rhizobia or nematodes, we identified genes from plant host, rhizobia, and nematode whose expression differed between parasite-infected and-uninfected plants, and between plants inoculated with different rhizobial strains. At the site of host-parasite interactions (in nematode galls), hundreds of host genes and few nematode genes differed in expression between host plants inoculated with different rhizobia strains. At the site of host-mutualist interactions (in rhizobia nodules), hundreds of host genes and few rhizobial genes responded to parasite infection. The vast majority of parasite-induced changes in host gene expression depended on the resident rhizobia strain. We additionally observed differences in parasite load and in some root architecture traits between plants inoculated with different rhizobia strains, showing that genetic variation in a mutualistic symbiont impacted parasite colonization. The transcriptomic and phenotypic differences we observed suggest that microbial indirect genetic effects play an underappreciated role in their hosts interactions with other co-colonizing microorganisms.

ecology↗
bioRxiv2023

Mutualist-Provided Resources Increase Susceptibility to Parasites

Background and AimsO_LIMutualistic microbes often increase their hosts susceptibility to parasite infection, but the mechanism underlying this pattern remains unknown. C_LIO_LIWe tested two competing hypotheses to identify the cause of this phenomenon. C_LIO_LIFirst, mutualist-provided resources could attract antagonists by making hosts more resource-rich. C_LIO_LISecond, mutualism establishment itself might increase host vulnerability to antagonists by enabling antagonists to exploit host defenses or immune systems, which are often downregulated during mutualism establishment. C_LI MethodsO_LITo test which mechanism underlies increased parasite susceptibility, we experimentally decoupled mutualism establishment and mutualist-provided resources in the legume-rhizobia mutualism. C_LIO_LIWe measured parasite load on Medicago truncatula plants infected with root-knot nematodes in a full-factorial design, in which we independently manipulated rhizobia inoculation (mutualism establishment) and nitrogen availability (mutualist-provided resources). C_LI Key ResultsO_LIIncreased nitrogen availability increased parasite infection. However, its effect was non-linear and was not explained by nitrogen assimilation into plant tissues, indicating that this effect is not driven by parasite attraction to resource-rich hosts. C_LIO_LIWe found little effect of mutualism establishment on susceptibility, as neither rhizobia inoculation nor nodulation without nitrogen fixation significantly increased parasite infection. C_LI ConclusionsO_LIOur results suggest that mutualist-provided resources are an important driver of indirect ecological costs of mutualism, although the mechanism linking mutualist-provided resources and susceptibility to infection remains unknown. C_LI

ecology↗
bioRxiv2022

IMPASTO: Multiplexed cyclic imaging without signal removal via self-supervised neural unmixing

Spatially resolved proteomics requires a highly multiplexed imaging modality. Cyclic imaging techniques, which repeat staining, imaging, and signal erasure, have been adopted for this purpose. However, due to tissue distortion, it is challenging to obtain high fluorescent signal intensities and complete signal erasure in thick tissue with cyclic imaging techniques. Here, we propose an "erasureless" cyclic imaging method named IMPASTO. In IMPASTO, specimens are iteratively stained and imaged without signal erasure. Then, images from two consecutive rounds are unmixed to retrieve the images of single proteins through self-supervised machine learning without any prior training. Using IMPASTO, we demonstrate 30-plex imaging from brain slices in 10 rounds, and when used in combination with spectral unmixing, in five rounds. We show that IMPASTO causes negligible tissue distortion and demonstrate 3D multiplexed imaging of brain slices. Further, we show that IMPASTO can shorten the signal removal processes of existing cyclic imaging techniques.

bioengineering↗
bioRxiv2022

Elucidating the patterns of pleiotropy and its biological relevance in maize

Pleiotropy - when a single gene controls two or more seemingly unrelated traits - has been shown to impact genes with effects on flowering time, leaf architecture, and inflorescence morphology in maize. However, the genome-wide impact of true biological pleiotropy across all maize phenotypes is largely unknown. Here we investigate the extent to which biological pleiotropy impacts phenotypes within maize through GWAS summary statistics reanalyzed from previously published metabolite, field, and expression phenotypes across the Nested Association Mapping population and Goodman Association Panel. Through phenotypic saturation of 120,597 traits, we obtain over 480 million significant quantitative trait nucleotides. We estimate that only 1.56-32.3% of intervals show some degree of pleiotropy. We then assessed the relationship between pleiotropy and various biological features such as gene expression, chromatin accessibility, sequence conservation, and enrichment for gene ontology terms. We find very little relationship between pleiotropy and these variables when compared to permuted pleiotropy. We hypothesize that biological pleiotropy of common alleles is not widespread in maize and is highly impacted by nuisance terms such as population structure and linkage disequilibrium. Natural selection on large standing natural variation in maize populations may target wide- and large-effect variants, leaving the prevalence of detectable pleiotropy relatively low. Author SummaryThe genetic basis of complex traits has been thought to exhibit pleiotropy, which is the notion that a single locus can control two or more unrelated traits. Widespread reports in the human disease literature show genomic signatures of pleiotropic loci across many traits. However, little is known about the prevalence and behavior of pleiotropy in maize across a large number of phenotypes. Using association mapping of common alleles in over one hundred thousand traits, we determine how pleiotropic each region was and use these quantitative scores to functionally characterize each region of the genome. Our results show little evidence that pleiotropy is a common phenomenon in maize. We observed that maize does not exhibit the same pleiotropic characteristics as human diseases in terms of prevalence, gene expression, chromatin accessibility, or sequence conservation. Rather than pervasive pleiotropy, we hypothesize that strong selection on large and wide effect loci and the need for trait independence at the gene level keep the prevalence of pleiotropy low, thus, allowing for the adaptation of maize varieties to novel environments and conditions.

plant biology↗
bioRxiv2020

Live-cell imaging shows uneven segregation of extrachromosomal DNA elements and transcriptionally active extrachromosomal DNA clusters in cancer

Oncogenic extrachromosomal DNA elements (ecDNAs) promote intratumoral heterogeneity, creating a barrier for successful cancer treatments. The underlying mechanisms are poorly understood and studies are hampered in part by a lack of adequate tools enabling studies of ecDNA behavior. Here, we show that single-cell ecDNA copy numbers follow a Gaussian distribution across tumor cells in vitro and in patient glioblastoma specimens, suggesting uneven ecDNA segregation during mitosis. We established a CRISPR-based approach which leverages unique ecDNA breakpoint sequences to tag ecDNA with fluorescent markers in living cells. Applying this method during mitosis revealed disjointed ecDNA inheritance patterns, providing an explanation for rapid ecDNA accumulation in cancer. Post-mitosis, ecDNAs tended to cluster and clustered ecDNAs colocalized with RNA polymerase II, promoting transcription of cargo oncogenes. Our observations provide direct evidence for uneven segregation of ecDNA and shed new lights of mechanisms through which ecDNAs contribute to oncogenesis.

cancer biology↗
bioRxiv2020

Single-cell multimodal glioma analyses reveal epigenetic regulators of cellular plasticity and environmental stress response

Glioma intratumoral heterogeneity enables adaptation to challenging microenvironments and contributes to universal therapeutic resistance. Here, we integrated 914 single-cell DNA methylomes, 55,284 single-cell transcriptomes, and bulk multi-omic profiles across 11 adult IDH-mutant or IDH-wild-type gliomas to delineate sources of intratumoral heterogeneity. We found that local DNA methylation instability, or epimutation burden, was elevated in more aggressive tumors, reflected intratumoral variability, linked with transcriptional disruption, and associated with environmental stress response. We show that the activation of cell-state specific transcription factors is impacted by epimutations and that loosened epigenetic control may facilitate cellular plasticity. Our analyses support that somatic copy number alterations (SCNAs) promote epigenetic instability and that SCNAs largely precede epigenetic and transcriptomic diversification during glioma evolution. We confirmed the link between genetic and epigenetic instability by analyzing larger cohorts of bulk longitudinally collected and spatially separated DNA methylation data. Increased DNA methylation instability was associated with accelerated disease progression, and recurrently selected DNA methylation changes were enriched for environmental stress response pathways. Our work provides an integrative framework to better understand glioma evolution and highlights the importance of epigenetic heterogeneity in shaping therapeutic response.

cancer biology↗