arXiv subjects

Antonio Culla

Publications and source records attributed to Antonio Culla.

5 recordsLinked to original sources

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↗

arXiv2023

Renormalization group study of marginal ferromagnetism

When studying the collective motion of biological groups a useful theoretical framework is that of ferromagnetic systems, in which the alignment interactions are a surrogate of the effective imitation among the individuals. In this context, the experimental discovery of scale-free correlations of speed fluctuations in starling flocks poses a challenge to the common statistical physics wisdom, as in the ordered phase of standard ferromagnetic models with $\mathrm{O}(n)$ symmetry, the modulus of the order parameter has finite correlation length. To make sense of this anomaly a novel ferromagnetic theory has been proposed, where the bare confining potential has zero second derivative (i.e.\ it is marginal) along the modulus of the order parameter. The marginal model exhibits a zero-temperature critical point, where the modulus correlation length diverges, hence allowing to boost both correlation and collective order by simply reducing the temperature. Here, we derive an effective field theory describing the marginal model close to the $T=0$ critical point and calculate the renormalization group equations at one loop within a momentum shell approach. We discover a non-trivial scenario, as the cubic and quartic vertices do not vanish in the infrared limit, while the coupling constants effectively regulating the exponents $ν$ and $η$ have upper critical dimension $d_c=2$, so that in three dimensions the critical exponents acquire their free values, $ν=1/2$ and $η=0$. This theoretical scenario is verified by a Monte Carlo study of the modulus susceptibility in three dimensions, where the standard finite-size scaling relations have to be adapted to the case of $d>d_c$. The numerical data fully confirm our theoretical results.

cond-mat.stat-mech↗

arXiv2022

Marginal speed confinement resolves the conflict between correlation and control in natural flocks of birds

Speed fluctuations of individual birds in natural flocks are moderate, due to the aerodynamic and biomechanical constraints of flight. Yet the spatial correlations of such fluctuations are scale-free, namely they have a range as wide as the entire group, a property linked to the capacity of the system to collectively respond to external perturbations. Scale-free correlations and moderate fluctuations set conflicting constraints on the mechanism controlling the speed of each agent, as the factors boosting correlation amplify fluctuations, and vice versa. Here, using a statistical field theory approach, we suggest that a marginal speed confinement that ignores small deviations from the natural reference value while ferociously suppressing larger speed fluctuations, is able to reconcile scale-free correlations with biologically acceptable group's speed. We validate our theoretical predictions by comparing them with field experimental data on starling flocks with group sizes spanning an unprecedented interval of over two orders of magnitude.

cond-mat.stat-mech↗

arXiv2019

Low-temperature marginal ferromagnetism explains anomalous scale-free correlations in natural flocks

We introduce a new ferromagnetic model capable of reproducing one of the most intriguing properties of collective behaviour in starling flocks, namely the fact that strong collective order of the system coexists with scale-free correlations of the modulus of the microscopic degrees of freedom, that is the birds' speeds. The key idea of the new theory is that the single-particle potential needed to bound the modulus of the microscopic degrees of freedom around a finite value, is marginal, that is has zero curvature. We study the model by using mean-field approximation and Monte Carlo simulations in three dimensions, complemented by finite-size scaling analysis. While at the standard critical temperature, $T_c$, the properties of the marginal model are exactly the same as a normal ferromagnet with continuous symmetry-breaking, our results show that a novel zero-temperature critical point emerges, so that in its deeply ordered phase the marginal model develops divergent susceptibility and correlation length of the modulus of the microscopic degrees of freedom, in complete analogy with experimental data on natural flocks of starlings.

cond-mat.stat-mech↗