Biology subjects

Drucker, M.

Publications and source records attributed to Drucker, M..

4 recordsLinked to original sources

bioRxiv2024

Genotype-immunophenotype relationships in NPM1-mutant AML clonal evolution uncovered by single cell multiomic analysis

Acute myeloid leukemia (AML) is a multi-clonal disease, existing as a milieu of clones with unique but related genotypes as initiating clones acquire subsequent mutations. However, bulk sequencing cannot fully capture AML clonal architecture or the clonal evolution that occurs as patients undergo therapy. To interrogate clonal evolution, we performed simultaneous single cell molecular profiling and immunophenotyping on 43 samples from 32 NPM1-mutant AML patients at different stages of disease. Here we show that diagnosis and relapsed AML samples display similar clonal architecture patterns, but signaling mutations can drive increased clonal diversity specifically at relapse. We uncovered unique genotype-immunophenotype relationships regardless of disease state, suggesting leukemic lineage trajectories can be hard-wired by the mutations present. Analysis of longitudinal samples from patients on therapy identified dynamic clonal, transcriptomic, and immunophenotypic changes. Our studies provide resolved understanding of leukemic clonal evolution and the relationships between genotype and cell state in leukemia biology.

cancer biology↗

bioRxiv2024

Interplay between a polerovirus and a closterovirus decreases transmission of the polerovirus

Multi-infection of plant by viruses is very common and can change drastically infection parameters such as virus accumulation, distribution and vector transmission. Sugar beet is an important crop that is frequently co-infected by the polerovirus beet chlorosis virus (BChV) and the closterovirus beet yellows virus (BYV), both vectored by the green peach aphid (Myzus persicae). These phloem-limited viruses are acquired while aphids ingest phloem sap from infected plants. Here we found that co-infection decreased transmission of BChV by [~]50%, but had no impact on BYV transmission. The drastic reduction of BChV transmission was not due to lower accumulation of BChV in co-infected plants, nor to reduced phloem sap ingestion by aphids from these plants. Using the SABER-FISH in situ hybridization technique on plants, we observed that 40% of the infected phloem cells were co-infected and that co-infection caused redistribution of BYV in these cells. The BYV accumulation pattern changed from distinct intracellular spherical inclusions in mono-infected cells to a diffuse form in co-infected cells. There, BYV co-localized with BChV throughout the cytoplasm, indicative of virus-virus interactions. We propose that BYV-BChV interactions could restrict BChV access to the sieve tubes and reduce its accessibility for aphids and present a model of how co-infection could alter BChV intracellular movement and/or phloem loading and reduce BChV transmission. IMPORTANCEMixed viral infections in plants are understudied yet can have significant influences on disease dynamics and virus transmission. We investigated how co-infection with two unrelated viruses, beet chlorosis virus (BChV) and beet yellows virus (BYV), affects aphid transmission of the viruses in sugar beet plants. We show that co-infection reduced BChV transmission by about 50% without affecting BYV transmission, despite similar virus accumulation rates in co-infected and mono-infected plants. Follow-up experiments examined the localization and intra-cellular distribution of the viruses, leading to the discovery that co-infection caused a redistribution of BYV in the phloem vessels and altered its repartition pattern within plant cells, suggesting virus-virus interactions. In conclusion, the interplay between BChV and BYV affects the transmission of BChV but not BYV, possibly through direct or indirect virus-virus interactions at the cellular level. Understanding these interactions could be crucial for managing virus propagation in crops and preventing yield losses.

plant biology↗

bioRxiv2022

Transcriptome responses of virus-transmitting aphid vectors are shaped by the host plant and the virus mode of transmission

BackgroundNumerous studies have documented modifications in vector orientation behavior, settling and feeding behavior, and/or fecundity and survival due to virus infection in host plants. These alterations are often expected to enhance virus transmission, which has led to the hypothesis that such effects are vector manipulations by the virus. However, until now, the gene expression changes correlating with these effects and indicative of modified vector pathways and mechanisms are mostly unknown. ResultsTranscriptome profiling of Myzus persicae aphids feeding on turnip yellows virus (TuYV) and cauliflower mosaic virus (CaMV) infected Arabidopsis thaliana and Camelina sativa revealed a substantial proportion of commonly deregulated genes, amongst them many with general functions in plant-virus-aphid interactions. We identified also aphid genes specifically deregulated by CaMV or TuYV infection, which might be related to the viral transmission mode. Furthermore, we observed strong host-specific differences in the gene expression patterns with plant virus infection causing more deregulations of aphid genes on A. thaliana than on C. sativa, likely related to the differences in susceptibility of the plant hosts to these viruses. Finally, stress-related aphid genes were downregulated in M. persicae on both infected plants, regardless of the virus. ConclusionsTuYV, relying on the circulative persistent mode of transmission, tended to affect developmental genes. This could increase the proportion of alate aphids, but also affect their locomotion, neuronal activity, and lifespan. CaMV, using the non-circulative non-persistent mode of transmission, had a strong impact on feeding-related genes and in particular those related to salivary proteins. In general, these transcriptome alterations targeted pathways that seem to be particularly adapted to the transmission mode of the corresponding virus and could be evidence of vector manipulation by the virus.

plant biology↗

bioRxiv2022

Comparative plant transcriptome profiling of Arabidopsis and Camelina infested with Myzus persicae aphids acquiring circulative and non-circulative viruses reveals virus- and plant-specific alterations relevant to aphid feeding behavior and transmission

BackgroundEvidence accumulates that plant viruses alter host-plant traits in ways that modify their insect vectors behavior. These alterations often enhance virus transmission, which has led to the hypothesis that these effects are manipulations caused by viral adaptation. However, the genetic basis of these indirect, plant-mediated effects on vectors and their dependence on the plant host and the mode of virus transmission is hardly known. ResultsTranscriptome profiling of Arabidopsis thaliana and Camelina sativa plants infected with turnip yellows virus (TuYV) or cauliflower mosaic virus (CaMV) and infested with the common aphid vector Myzus persicae revealed strong virus- and host-specific differences in the gene expression patterns. CaMV infection caused more severe effects on the phenotype of both plant hosts than did TuYV infection, and the severity of symptoms correlated strongly with the proportion of differentially expressed genes, especially photosynthesis genes. Accordingly, CaMV infection modified aphid behavior and fecundity stronger than did infection with TuYV. ConclusionsOverall, infection with CaMV - relying on the non-circulative transmission mode - tends to have effects on metabolic pathways with strong potential implications for insect-vector / plant-host interactions (e.g. photosynthesis, jasmonic acid, ethylene and glucosinolate biosynthetic processes), while TuYV - using the circulative transmission mode - alters these pathways only weakly. These virus-induced deregulations of genes that are related to plant physiology and defense responses might impact aphid probing and feeding behavior on both infected host plants, with potentially distinct effects on virus transmission.

plant biology↗