Promoters architecture-based mechanism for noise-induced oscillations in a single-gene circuit

It is well known that single-gene circuits with negative feedback loop can lead to oscillatory gene expression when they operate with time delay. In order to generate these oscillations many processes can contribute to properly timing such delay. Here we show that the time delay coming from the transitions between internal states of the cis-regulatory system (CRS) can drive sustained oscillations in an auto-repressive single-gene circuit operating in a small volume like a cell. We found that the cooperative binding of repressor molecules is not mandatory for a oscillatory behavior if there are enough binding sites in the CRS. These oscillations depend on an adequate balance between the CRS kinetic, and the synthesis/ degradation rates of repressor molecules. This finding suggest that the multi-site CRS architecture can play a key role for oscillatory behavior of gene expression. Finally, our results can also help to synthetic biologists on the design of the promoters architecture for new genetic oscillatory circuits.Instituto de Física de Líquidos y Sistemas BiológicosFacultad de Ciencias ExactasCentro Regional de Estudios Genómico

Interfacial properties in a discrete model for tumor growth

We propose and study, by means of Monte Carlo numerical simulations, a minimal discrete model for avascular tumor growth, which can also be applied for the description of cell cultures in vitro. The interface of the tumor is self-affine and its width can be characterized by the following exponents: (i) the growth exponent β = 0.32 ( 2 ) that governs the early time regime, (ii) the roughness exponent α = 0.49 ( 2 ) related to the fluctuations in the stationary regime, and (iii) the dynamic exponent z = α / β ≃ 1.49 ( 2 ) , which measures the propagation of correlations in the direction parallel to the interface, e.g., ξ ∝ t 1 / z , where ξ is the parallel correlation length. Therefore, the interface belongs to the Kardar-Parisi-Zhang universality class, in agreement with recent experiments of cell cultures in vitro. Furthermore, density profiles of the growing cells are rationalized in terms of traveling waves that are solutions of the Fisher-Kolmogorov equation. In this way, we achieved excellent agreement between the simulation results of the discrete model and the continuous description of the growth front of the culture or tumor.Fil: Moglia, Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; ArgentinaFil: Guisoni, Nara Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; ArgentinaFil: Albano, Ezequiel Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentin

Origins: A protein network-based approach to quantify cell pluripotency from scRNA-seq data

Trajectory inference is a common application of scRNA-seq data. However, it is often necessary to previously determine the origin of the trajectories, the stem or progenitor cells. In this work, we propose a computational tool to quantify pluripotency from single cell transcriptomics data. This approach uses the protein-protein interaction (PPI) network associated with the differentiation process as a scaffold and the gene expression matrix to calculate a score that we call differentiation activity. This score reflects how active the differentiation network is in each cell. We benchmark the performance of our algorithm with two previously published tools, LandSCENT (Chen et al., 2019) and CytoTRACE (Gulati et al., 2020), for four healthy human data sets: breast, colon, hematopoietic and lung. We show that our algorithm is more efficient than LandSCENT and requires less RAM memory than the other programs. We also illustrate a complete workflow from the count matrix to trajectory inference using the breast data set. • ORIGINS is a methodology to quantify pluripotency from scRNA-seq data implemented as a freely available R package. • ORIGINS uses the protein-protein interaction network associated with differentiation and the data set expression matrix to calculate a score (differentiation activity) that quantifies pluripotency for each cell.Fil: Senra, Daniela. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Guisoni, Nara Cristina. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Pinning-depinning transition in a stochastic growth model for the evolution of cell colony fronts in a disordered medium

We study a stochastic lattice model for cell colony growth, which takes into account proliferation, diffusion, and rotation of cells, in a culture medium with quenched disorder. The medium is composed both by sites that inhibit any possible change in the internal state of the cells, representing the disorder, as well as by active medium sites, that do not interfere with the cell dynamics. By means of Monte Carlo simulations we find that the velocity of the growing interface, which is taken as the order parameter of the model, strongly depends on the density of active medium sites ($ho_A$). In fact, the model presents a (continuous) second-order pinning-depinning transition at a certain critical value of $ho_A^{crit}$, such as for $ho_A>ho_A^{crit}$ the interface moves freely across the disordered medium, but for $ho_AFil: Moglia, Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina. Fundación Centro de Medicina Nuclear y Molecular Entre Ríos. Departamento de Física Médica; ArgentinaFil: Albano, Ezequiel Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; ArgentinaFil: Guisoni, Nara Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentin

Pinning-depinning transition in a stochastic growth model for the evolution of cell colony fronts in a disordered medium

We study a stochastic lattice model for cell colony growth, which takes into account proliferation, diffusion, and rotation of cells, in a culture medium with quenched disorder. The medium is composed both by sites that inhibit any possible change in the internal state of the cells, representing the disorder, as well as by active medium sites, that do not interfere with the cell dynamics. By means of Monte Carlo simulations we find that the velocity of the growing interface, which is taken as the order parameter of the model, strongly depends on the density of active medium sites (ρA). In fact, the model presents a (continuous) second-order pinning-depinning transition at a certain critical value of ρ crit A , such as for ρA > ρcritcrit A the interface becomes irreversible pinned by the disorder. By determining the relevant critical exponents, our study reveals that within the depinned phase the interface can be rationalized in terms of the Kardar-Parisi-Zhang universality class, but when approaching the critical threshold, the non-linear term of the Kardar-Parisi-Zhang equation tends to vanish and then the pinned interface belongs to the quenched Edwards-Wilkinson universality class.Instituto de Física de Líquidos y Sistemas Biológico

Interfacial properties in a discrete model for tumor growth

We propose and study, by means of Monte Carlo numerical simulations, a minimal discrete model for avascular tumor growth, which can also be applied for the description of cell cultures in vitro. The interface of the tumor is self-affine and its width can be characterized by the following exponents: (i) the growth exponent β = 0.32 ( 2 ) that governs the early time regime, (ii) the roughness exponent α = 0.49 ( 2 ) related to the fluctuations in the stationary regime, and (iii) the dynamic exponent z = α / β ≃ 1.49 ( 2 ) , which measures the propagation of correlations in the direction parallel to the interface, e.g., ξ ∝ t 1 / z , where ξ is the parallel correlation length. Therefore, the interface belongs to the Kardar-Parisi-Zhang universality class, in agreement with recent experiments of cell cultures in vitro. Furthermore, density profiles of the growing cells are rationalized in terms of traveling waves that are solutions of the Fisher-Kolmogorov equation. In this way, we achieved excellent agreement between the simulation results of the discrete model and the continuous description of the growth front of the culture or tumor.Instituto de Física de Líquidos y Sistemas BiológicosConsejo Nacional de Investigaciones Científicas y Técnica

Promoters Architecture-Based Mechanism for Noise-Induced Oscillations in a Single-Gene Circuit

It is well known that single-gene circuits with negative feedback loop can lead to oscillatory gene expression when they operate with time delay. In order to generate these oscillations many processes can contribute to properly timing such delay. Here we show that the time delay coming from the transitions between internal states of the cis-regulatory system (CRS) can drive sustained oscillations in an auto-repressive single-gene circuit operating in a small volume like a cell. We found that the cooperative binding of repressor molecules is not mandatory for a oscillatory behavior if there are enough binding sites in the CRS. These oscillations depend on an adequate balance between the CRS kinetic, and the synthesis/degradation rates of repressor molecules. This finding suggest that the multi-site CRS architecture can play a key role for oscillatory behavior of gene expression. Finally, our results can also help to synthetic biologists on the design of the promoters architecture for new genetic oscillatory circuits.Fil: Guisoni, Nara Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; ArgentinaFil: Monteoliva, D.. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física; ArgentinaFil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Modeling active cell movement with the Potts model

In the last decade, the cellular Potts model has been extensively used to model interacting cell systems at the tissue-level. However, in early applications of this model, cell movement was taken as a consequence of membrane fluctuations due to cell-cell interactions, or as a response to an external chemotactic gradient. Recent findings have shown that eukaryotic cells can exhibit persistent displacements across scales larger than cell size, even in the absence of external signals. Persistent cell motion has been incorporated to the cellular Potts model by many authors in the context of collective motion, chemotaxis and morphogenesis. In this paper, we use the cellular Potts model in combination with a random field applied over each cell. This field promotes a uniform cell motion in a given direction during a certain time interval, after which the movement direction changes. The dynamics of the direction is coupled to a first order autoregressive process. We investigated statistical properties, such as the mean-squared displacement and spatio-temporal correlations, associated to these self-propelled in silico cells in different conditions. The proposed model emulates many properties observed in different experimental setups. By studying low and high density cultures, we find that cell-cell interactions decrease the effective persistent time.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasCentro Regional de Estudios Genómico