Biology subjects

Khoury, H.

Publications and source records attributed to Khoury, H..

5 recordsLinked to original sources

bioRxiv2026

Pan-cancer analysis of single-cell RNA sequencing data from 304 human tumors sheds light on the aneuploidy paradox

Aneuploidy poses a central paradox in cancer biology: it impairs cellular fitness in normal cells but drives cancer progression. To resolve this, we analyzed single cell transcriptomes from >665,000 cells - including [~]288,000 malignant cells - across 304 tumors and 15 cancer types. Integrating transcriptomics with inferred aneuploidy profiles, we characterized cell-intrinsic programs and interactions with the tumor microenvironment. Unexpectedly, highly aneuploid single cells exhibited reduced proliferation and metabolism, contrasting sharply with tumor-bulk profiles. We show this divergence is driven by karyotypic heterogeneity: in highly heterogeneous tumors, aneuploid cells display signatures of acute stress and negative selection. Conversely, in clonally aneuploid tumors, these detrimental signatures are lost and replaced by signatures of increased proliferation and enhanced metabolism, reflecting adaptation. Additionally, we identified consistent transcriptional programs driven by recurrent chromosome-arm alterations across both single cells and bulk tumors. These findings illuminate the selective forces shaping tumor evolution and the aneuploidy paradox. Statement Of SignificanceBy jointly evaluating gene expression and aneuploidy at single-cell resolution, we demonstrate that karyotypic heterogeneity underlies the transcriptional impact of aneuploidy, reveal distinct cellular responses to emerging versus stable states, and identify recurrent chromosomal alterations that drive conserved transcriptional programs. Our findings capture the dynamics of aneuploidy evolution in human tumors, providing novel insights into the aneuploidy paradox.

cancer biology↗

bioRxiv2025

Pan-cancer analysis reveals genomic fidelity and evolution of patient-derived organoids

BackgroundPatient-derived organoids (PDOs) are gaining recognition as a promising ex vivo model for cancer research, offering advantages over traditional 2D cell lines by better recapitulating tumor biology. ResultsIn this study, we assess the genomic stability and evolution of PDOs by analyzing copy-number alterations (CNAs) in 300 PDO samples across 16 cancer types. These results are compared with data from previously analyzed patient-derived xenografts (PDXs). We observe that PDOs exhibit genomic evolution over passaging, with an increasing divergence from the original tumor genome over time. Importantly, across cancer types, PDOs maintain higher genomic fidelity and are more genetically similar to their tumors of origin than PDX models. Moreover, PDOs show greater genomic stability during culture passaging compared to PDXs. ConclusionsThese findings position PDOs as a reliable and representative model for cancer research, while highlighting the need to carefully track their genomic evolution in culture.

cancer biology↗

bioRxiv2024

ASTROGLIOSIS AND NEUROINFLAMMATION UNDERLIE SCOLIOSIS UPON CILIA DYSFUNCTION

Cilia defects lead to scoliosis in zebrafish, but the underlying pathogenic mechanisms are poorly understood and may diverge depending on the mutated gene. Here, we dissected the mechanisms of scoliosis onset in a zebrafish mutant for the rpgrip1l gene encoding a ciliary transition zone protein. rpgrip1l mutant fish developed scoliosis with near-total penetrance but asynchronous onset in juveniles. Taking advantage of this asynchrony, we found that curvature onset was preceded by ventricle dilations and was concomitant to the perturbation of Reissner fiber polymerization and to the loss of multiciliated tufts around the subcommissural organ. Rescue experiments showed that Rpgrip1l was exclusively required in foxj1a-expressing cells to prevent axis curvature. Genetic interactions investigations ruled out Urp1/2 levels as a main driver of scoliosis in rpgrip1 mutants. Transcriptomic and proteomic studies identified neuroinflammation associated with increased Annexin levels as a potential mechanism of scoliosis development in rpgrip1l juveniles. Investigating the cell types associated with annexin2 over-expression, we uncovered astrogliosis, arising in glial cells surrounding the diencephalic and rhombencephalic ventricles just before scoliosis onset and increasing with time in severity. Anti-inflammatory drug treatment reduced scoliosis penetrance and severity and this correlated with reduced astrogliosis and macrophage/microglia enrichment around the diencephalic ventricle. Mutation of the cep290 gene encoding another transition zone protein also associated astrogliosis with scoliosis. Thus, we propose astrogliosis induced by perturbed ventricular homeostasis and associated with immune cell activation as a novel pathogenic mechanism of zebrafish scoliosis caused by cilia dysfunction.

developmental biology↗

bioRxiv2019

Genome wide identification of NAC transcription factors and their role in abiotic stress tolerance in Chenopodium quinoa

Chenopodium quinoa Willd. (quinoa) is a pseudocereal with high nutritional value and relatively high tolerance to several abiotic stresses, including water deficiency and salt stress, making it a suitable plant for the study of mechanisms of abiotic stress tolerance. NAC (NAM, ATAF and CUC) transcription factors are involved in a range of plant developmental processes and in the response of plants to biotic and abiotic stresses. In the present study, we perform a genome-wide comprehensive analysis of the NAC transcription factor gene family in quinoa. In total, we identified 107 quinoa NAC transcription factor genes, distributed equally between sub-genomes A and B. They are phylogenetically clustered into two major groups and 18 subgroups. Almost 75% of the identified CqNAC genes were duplicated two to seven times and the remaining 25% of the CqNAC genes were found as a single copy. We analysed the transcriptional responses of the identified quinoa NAC TF genes in response to various abiotic stresses. The transcriptomic data revealed 28 stress responsive CqNAC genes, where their expression significantly changed in response to one or more abiotic stresses, including salt, water deficiency, heat and phosphate starvation. Among these stress responsive NACs, some were previously known to be stress responsive in other species, indicating their potentially conserved function in response to abiotic stress across plant species. Six genes were differentially expressed specifically in response to phosphate starvation but not to other stresses, and these genes may play a role in controlling plant responses to phosphate deficiency. These results provide insights into quinoa NACs that could be used in the future for genetic engineering or molecular breeding.

plant biology↗

bioRxiv2019

The quail as an avian model system: its genome provides insights into social behaviour, seasonal biology and infectious disease response

The Japanese quail (Coturnix japonica) is a popular domestic poultry species and an increasingly significant model species in avian developmental, behavioural and disease research. We have produced a high-quality quail genome sequence, spanning 0.93 Gb assigned to 33 chromosomes. In terms of contiguity, assembly statistics, gene content and chromosomal organization, the quail genome shows high similarity to the chicken genome. We demonstrate the utility of this genome through three diverse applications. First, we identify selection signatures and candidate genes associated with social behaviour in the quail genome, an important agricultural and domestication trait. Second, we investigate the effects and interaction of photoperiod and temperature on the transcriptome of the quail medial basal hypothalamus, revealing key mechanisms of photoperiodism. Finally, we investigate the response of quail to H5N1 influenza infection. In quail lung, many critical immune genes and pathways were downregulated, and this may be key to the susceptibility of quail to H5N1. This genome will facilitate further research into diverse research questions using the quail as a model avian species.

genomics↗