arXiv subjects

Domenico Caudo

Publications and source records attributed to Domenico Caudo.

5 recordsLinked to original sources

arXiv2026

How genome redundancy can promote evolutionary innovation

Polyploidy is defined as the existence of more than two complete sets of homologous chromosomes. Despite it being a widespread phenomenon across the tree of life, its role as either an evolutionary innovation or a dead end is still debated. Here, we investigate how under varying selective pressures the degree of ploidy interacts with two key biological factors: the mode of inheritance and the genotype-phenotype mapping. Through a minimal evolutionary model we find that polyploidy is especially advantageous during abrupt environmental changes, confirming that polyploidization is often associated with ecological upheavals. We observe that stochastic inheritance combined with a nonlinear (maximum-based) genotype-phenotype mapping maximizes both phenotypic exploitation and landscape exploration across all environments. By contrast, structured inheritance with an additive phenotype mapping systematically underperforms, yet displays a pronounced optimum at low-to-intermediate ploidy level that mirrors the distribution observed in natural plant and bacterial populations. When individuals are free to carry different chromosome numbers, selection drives the population toward values that reflect an interplay between exploitation, exploration, and convergence speed rather than any single evolutionary objective. The relative weight of these three factors depends on the fitness landscape, providing a unifying framework for understanding when and why polyploidy is favored by natural selection.

q-bio.PE↗

arXiv2026

VertAX: a differentiable vertex model for learning epithelial tissue mechanics

Epithelial tissues dynamically reshape through local mechanical interactions among cells, a process well captured by vertex models. Yet their many tunable parameters make inference and optimization challenging, motivating computational frameworks that flexibly model and learn tissue mechanics. We introduce VertAX, a differentiable JAX-based framework for vertex-modeling of confluent epithelia. VertAX provides automatic differentiation, GPU acceleration, and end-to-end bilevel optimization for forward simulation, parameter inference, and inverse mechanical design. Users can define arbitrary energy and cost functions in pure Python, enabling seamless integration with machine-learning pipelines. We demonstrate VertAX on three representative tasks: (i) forward modeling of tissue morphogenesis, (ii) mechanical parameter inference, and (iii) inverse design of tissue-scale behaviors. We benchmark three differentiation strategies-automatic differentiation, implicit differentiation, and equilibrium propagation-showing that the latter can approximate gradients using repeated forward, adjoint-free simulations alone, offering a simple route for extending inverse biophysical problems to non-differentiable simulators with limited additional engineering effort.

cs.LG↗

arXiv2025

Inheritance Entropy: A Model-Independent Method to Probe the Hereditary Structure of Cell Lineage Trees

Human bone marrow stromal cells (BMSC) include skeletal stem cells with ground-breaking therapeutic potential. However, BMSC colonies have very heterogeneous in vivo behaviour, due to their different potency; this unpredictability is the greatest hurdle to the development of skeletal regeneration therapies. Colony-level heterogeneity urges a fundamental question: how is it possible that one colony as a collective unit behaves differently from another one? If cell-to-cell variability were just an uncorrelated random process, a million cells in a transplant-bound colony would be enough to yield statistical homogeneity, hence washing out any colony-level traits. A possible answer is that the differences between two originating cells are transmitted to their progenies and collectively persist through an hereditary mechanism. But non-genetic inheritance remains an elusive notion, both at the experimental and at the theoretical level. Here, we prove that heterogeneity in the lineage topology of BMSC clonal colonies is determined by heritable traits that regulate cell-cycle exit. The cornerstone of this result is the definition of a novel entropy of the colony, which measures the hereditary ramifications in the distribution of inactive cells across different branches of the proliferation tree. We measure the entropy in 32 clonal colonies, obtained from single-cell lineage tracing experiments, and show that in the greatest majority of clones this entropy is decisively smaller than that of the corresponding non-hereditary lineage. This result indicates that hereditary epigenetic factors play a major role in determining cycle exit of bone marrow stromal cells.

physics.bio-ph↗

arXiv2025

Lineage topology, replication kinetics and cell cycle synchronization reveal regulated growth dynamics in human bone marrow stromal cell colonies

Bone marrow stromal cells (BMSC) -- which include skeletal stem cells -- are a promising tool in regenerative medicine. However, their heterogeneous and unpredictable in vivo behaviour remains a critical barrier preventing the development of standardized therapeutic approaches for skeletal tissue regeneration. Several studies have attempted to identify in vitro features that could correlate with the in vivo differentiation properties, yet the mechanisms ruling BMSC heterogeneity remain poorly understood. Here, using time-lapse imaging, we lineage-trace 32 single-cell-derived BMSC colonies through seven generations. We observe significant inter-colony and intra-colony heterogeneity in lineage topology (determined by the number of senescent or apoptotic cells) and in replicative kinetics (measured from proliferating cells only). Interestingly, topology and kinetics result strongly correlated, suggesting the existence of regulatory factors linking the non-dividing/apoptotic subpopulations with proliferating cells. Furthermore, BMSCs display highly synchronized cell cycles during early generations, indicating stage-specific regulatory mechanisms through which cells influence each other. By employing a non-interacting population growth model, we demonstrate that the observed synchronisation cannot be explained by an uncorrelated branching process; instead, cell-to-cell correlation of division times must exist. Our findings reveal fundamental mechanisms governing BMSC heterogeneity and growth dynamics that may inform strategies to control their regenerative potential.

q-bio.CB↗

arXiv2024

Robust assessment of asymmetric division in colon cancer cells

Asymmetric partition of fate determinants during cell division is a hallmark of cell differentiation. Recent work suggested that such a mechanism is hijacked by cancer cells to increase both their phenotypic heterogeneity and plasticity and in turn their fitness. To quantify fluctuations in the partitioning of cellular elements, imaging-based approaches are used, whose accuracy is limited by the difficulty of detecting cell divisions. Our work addresses this gap proposing a general method based on high-throughput flow cytometry measurements coupled with a theoretical framework. We applied our method to a panel of both normal and cancerous human colon cells, showing that different kinds of colon adenocarcinoma cells display very distinct extents of fluctuations in their cytoplasm partition, explained by an asymmetric division of their size. To test the accuracy of our population-level protocol, we directly measure the inherited fractions of cellular elements from extensive time-lapses of live-cell laser scanning microscopy, finding excellent agreement across the cell types. Ultimately, our flow cytometry-based method promises to be accurate and easily applicable to a wide range of biological systems where the quantification of partition fluctuations would help accounting for the observed phenotypic heterogeneity and plasticity

q-bio.CB↗