Biology subjects

Vigano', S.

Publications and source records attributed to Vigano', S..

5 recordsLinked to original sources

bioRxiv2025

Impact of Task Similarity and Training Regimes on Cognitive Transfer and Interference

Learning depends not only on the content of what we learn, but also on how we learn and on how experiences are structured over time. To investigate how task similarity and training regime interact during learning, we trained participants on spatial and conceptual learning tasks that shared either similar or distinct underlying structures, using either interleaved or blocked regimes. Interleaving the two tasks hindered performance when their structures were similar, compared to when they were different. In contrast, blocked training produced the opposite effect: it improved performance and facilitated transfer across similar tasks. This effect, however, emerged only when participants first learned the conceptual task, followed by the spatial task, suggesting an asymmetric interaction between task order and structural similarity. We also replicated our results using a neural network model, providing converging evidence for the computational principles governing the interplay between training regime and structural similarity in multi-task learning.

neuroscience↗

bioRxiv2025

The effects of task similarity during representation learning in brains and neural networks

The complexity of our environment poses significant challenges for adaptive behavior. Recognizing shared structures across tasks can theoretically improve learning through generalization. However, how such shared representations emerge and influence performance remains poorly understood. Contrary to expectations, our findings revealed that individuals trained on tasks with similar low-dimensional structures performed worse than those trained on dissimilar tasks. Magnetoencephalography revealed correlated neural representations in the samestructure group and anticorrelated ones in the different-structure group. Crucially, practice reduced this performance gap and shifted the neural representations of the tasks in the samestructure group towards anticorrelation, like those in the different-structure group. A neural network model trained on similar tasks replicated these findings: tasks with similar structures require more iterations to orthogonalize their representations. These results highlight a complex interplay between task similarity, neural dynamics, and behavior, challenging traditional assumptions about learning and generalization.

neuroscience↗

bioRxiv2023

Human aneuploid cells depend on the RAF/MEK/ERK pathway for overcoming increased DNA damage

Aneuploidy is a hallmark of human cancer, yet the cellular mechanisms that allow cells to cope with aneuploidy-induced cellular stresses remain largely unknown. Such coping mechanisms may present cellular vulnerabilities that can be harnessed for targeting cancer cells. Here, we induced aneuploidy in non-transformed RPE1-hTERT cells and derived multiple stable clones with various degrees of chromosome imbalances. We performed an unbiased genomic profiling of 6 isogenic clones, using whole-exome and RNA sequencing. We then functionally interrogated their cellular dependency landscapes, using genome-wide CRISPR/Cas9 screens and large-scale drug screens. We found that aneuploid clones activated the DNA damage response (DDR), and were consequently more resistant to further DNA damage induction. Interestingly, aneuploid cells also exhibited elevated RAF/MEK/ERK pathway activity, and were more sensitive to several clinically-relevant drugs targeting this pathway, and in particular to genetic and chemical CRAF inhibition. CRAF activity was functionally linked to the resistance to DNA damage induction, as CRAF inhibition sensitized aneuploid cells to DNA damage-inducing chemotherapies. The association between aneuploidy, RAF/MEK/ERK signaling, and DDR was independent of p53. The increased activity and dependency of aneuploid cells on the RAF/MEK/ERK pathway was validated in another isogenic aneuploid system, and across hundreds of human cancer cell lines, confirming their relevance to human cancer. Overall, our study provides a comprehensive resource for genetically-matched karyotypically-stable cells of various aneuploidy states, and reveals a novel therapeutically-relevant cellular dependency of aneuploid cells.

cancer biology↗

bioRxiv2023

Increased RNA and protein degradation is required for counteracting transcriptional burden and proteotoxic stress in human aneuploid cells

Aneuploidy, an abnormal chromosome composition, results in a stoichiometric imbalance of protein complexes, which jeopardizes the fitness of aneuploid cells. Aneuploid cells thus need to compensate for the imbalanced DNA levels by regulating their RNA and protein levels, a phenomenon known as dosage compensation. However, the molecular mechanisms involved in dosage compensation in human cells - and whether they can be targeted to selectively kill aneuploid cancer cells - remain unknown. Here, we addressed this question via molecular dissection of multiple diploid vs. aneuploid cell models. Using genomic and functional profiling of a novel isogenic system of RPE1-hTERT cells with various degrees of aneuploidy, we found that aneuploid cells cope with both transcriptional burden and proteotoxic stress. At the mRNA level, aneuploid cells increased RNA synthesis, but concomitantly elevated several RNA degradation pathways, in particular the nonsense-mediated decay (NMD) and the microRNA-mediated mRNA silencing pathways. Consequently, aneuploid cells were more sensitive to the genetic or chemical perturbation of several key components of these RNA degradation pathways. At the protein level, aneuploid cells experienced proteotoxic stress, resulting in reduced translation and increased protein degradation, rendering them more sensitive to proteasome inhibition. These findings were recapitulated across hundreds of human cancer cell lines and primary tumors, confirming that both non-transformed and transformed cells alter their RNA and protein metabolism in order to adapt to the aneuploid state. Our results reveal that aneuploid cells are dependent on the over- or under-activation of several nodes along the gene expression process, identifying these pathways as clinically-actionable vulnerabilities of aneuploid cells.

cancer biology↗

bioRxiv2020

Aneuploid cells activate NF-κB to promote their immune clearance by NK cells

SummaryThe immune system plays a major role in the protection against cancer. Identifying and characterizing the pathways mediating this immune surveillance is thus critical for understanding how cancer cells are recognized and eliminated. We previously found that untransformed cells that had undergone senescence due to highly abnormal karyotypes are eliminated by Natural Killer (NK) cells in vitro. Here we show that this is also true for aneuploid untransformed cells that had not lost their ability to proliferate. Their elimination by NK cells, like that of aneuploid senescent cells, is predominantly mediated by non-cell autonomous mechanisms. Our data further indicate that NF-κB signaling in aneuploid cells is central to eliciting this immune response. Inactivating NF-κB abolishes NK-cell mediated clearance in aneuploid cells in vitro. In cancer cell lines, NF-κB signaling correlates with degree of aneuploidy, raising the possibility that aneuploidy-induced immune recognition is partially retained in cancer.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗