Biology subjects

Lopez, J. I.

Publications and source records attributed to Lopez, J. I..

7 recordsLinked to original sources

bioRxiv2026

Systemic and kinematic properties of Amoeba proteus migration correlate strongly across environments

Recent work has shown that cell migration is a systemic property of the whole cell, yet how the different properties of a migratory trajectory relate to one another remains largely uncharacterized. Here we quantified the migration of 150 Amoeba proteus cells under three experimental scenarios (absence of stimuli, a direct-current electric field, and a chemotactic peptide gradient) with eleven metrics that describe either the systemic dynamics of the trajectory (long-range correlations, long-term persistence, super-diffusive exploration, regularity of the move steps and memory of the velocity) or its kinematic output (net displacement, straightness and speed). Screening all 55 metric pairs for statistical dependence with distance covariance identified six couplings that held in all three experimental scenarios, besides the pairs linked by definition. Long-term persistence and super-diffusive exploration were coupled with each other, in agreement with the scaling relation expected for self-similar trajectories, and each of them was coupled with the net displacement and the straightness of the trajectory: more persistent and more super-diffusive cells moved farther and along straighter paths. In addition, the long-range correlations of the move steps were coupled with the memory of speed between consecutive steps. All six couplings were positive and monotonic, with no trend reversal over the observed range. The stimuli shifted six of the eleven metrics, the electric field mainly increasing the straightness and the net displacement of the trajectories and the chemical gradient mainly increasing the speed memory, but they left the six couplings intact and reorganized part of the dependence structure around speed. These results show that several systemic and kinematic properties of Amoeba proteus migration are not independent observables but vary together as parts of an integrated system whose couplings are preserved across environments.

cell biology↗

bioRxiv2026

Quantifying the Information Capacity of DNA Methylation as an Epigenetic Memory System

The information content of the genome has been extensively analyzed. However, a comparable quantitative framework for DNA methylation is still lacking. Without such quantification, the magnitude of this regulatory and dynamic epigenetic structure remains conceptually imprecise, even though methylation dysregulation is strongly linked to disease-related phenotypes and altered cellular identity. Here we address this gap by applying Shannon information theory to DNA methylation. We first consider methylation marks as binary or probabilistic regulatory states and estimate the theoretical upper-bound information capacity of the human methylome under simplifying assumptions. We then progressively refine this estimate by incorporating biologically relevant constraints, including methylation bias, bimodal methylation distributions, local CpG correlation, genomic regulatory class, and cell-type-discriminative methylation patterns. This approach allows us to distinguish between theoretical methylation capacity, statistical methylation entropy, and biologically interpretable regulatory information. Finally, we consider methylation information from a discriminative perspective, analyzing its contribution to distinguishing cell types and regulatory cellular states. Within this framework, mutual information between methylation patterns and cell identity provides a biologically constrained estimate of methylations role as an epigenetic identity code. Our layered analysis reconciles megabit-scale methylome capacity with compact, biologically interpretable identity signatures. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/735086v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@44dc66org.highwire.dtl.DTLVardef@e1ba03org.highwire.dtl.DTLVardef@17b2acborg.highwire.dtl.DTLVardef@136b1ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2025

Transcriptional network analysis of PTEN protein-deficient prostate tumors reveals robust stromal reprogramming and signs of senescent paracrine communication

Among the extensive genomic alterations in prostate cancer, the genomic deletion of PTEN stands out as one of the most consistently observed and confirmed alteration. PTEN loss in prostate tumors is primarily associated with cancer cell proliferation and survival through the activation of the PI3K-AKT-mTOR signalling pathway. However, its use as a robust biomarker in the clinical practice is hampered by the complex epigenetic, transcriptional and post-translational regulation. Here, we undertook an approach that combined in situ assessment of PTEN protein with transcriptional surrogates of its activity to gain insights into the downstream functional effects of PTEN loss in primary tumors. Our extensive bioinformatic analyses, including the integration with single-cell RNA-Seq approaches in a new clinical cohort, highlighted stroma remodeling as the major cancer cell-extrinsic process associated with PTEN loss. By applying similar computational strategy on the transcriptomic data generated from primary prostate tumors of genetically engineered Pten knock-out mouse models, we validated the causal role of Pten in the stromal reaction observed in clinical specimens. Mechanistically, we provide evidence for the activation of a paracrine program that encompasses enhanced TGF-{beta} signalling and that is compatible with the secretome of PTEN-deficient senescent cancer cells. Our study provides relevant biological context to the cellular and molecular alterations unleashed upon PTEN protein loss.

cancer biology↗

bioRxiv2024

Sex-specific thermoregulatory effects of estrogen signaling in Reprimo lineage cells

Estrogens have considerable impact on energy homeostasis and metabolic health. In mice, signaling through estrogen receptor alpha (ER) alters energy intake and multiple aspects of energy expenditure, effects that may be mediated by specific regions or neuronal sub-populations of the hypothalamus. This study investigates the function of ER in neurons of the lineage that expresses Rprm (Reprimo), a gene we previously linked to thermoregulation in females. Here, we engineered a novel ReprimoCre mouse to selectively knock out ER in Rprm lineage cells (Reprimo-specific estrogen receptor KO; RERKO) and report changes in core temperature in female mice, with no changes in movement or food intake. RERKO females have elevated brown adipose tissue (BAT) temperature and lower tail temperature relative to controls, suggesting increased heat production and reduced heat dissipation, respectively. Developmental expression of Rprm was detected in the brain, but not in BAT or white adipose tissue suggesting temperature changes may be mediated by the nervous system. To confirm centrally mediated effects on temperature, we ablated Rprm expressing cells in the mediobasal hypothalamus and observed a reduction in core temperature relative to controls. Taken together, these results indicate that estrogen signaling in the Rprm lineage is critical for thermoregulation, mainly through the modulation of brown adipose tissue thermogenesis in female, but not male, mice.

physiology↗

bioRxiv2024

Systemic migrations in enucleated cells

Directional locomotion is a fundamental characteristic of many cells with great relevance in essential physiological and human pathological processes. For decades, research efforts have focused on studying specific individual processes and their corresponding biomolecular components involved in cellular locomotion movements. However, the notion that migratory displacements are functionally integrated and regulated at the systemic level has never been recognized. Recently, we have shown that locomotion movements correspond to an emergent systemic behavior which depends on a complex integrated self-organized system carefully regulated at a global cellular level. Here, to study the forces driving the locomotion movement of the cell, and to corroborate the thesis on the systemic character of the cellular migratory responses we have carried out an extensive study of locomotion movements with enucleated cells (cytoplasts) belonging to Amoeba proteus. The migratory behavior of both enucleated and non-enucleated cells has been individually studied in four different scenarios: in absence of stimuli, under a galvanotactic field, in chemotactic gradient, and under very complex conditions such as simultaneous galvanotactic and chemotactic stimuli. All these experimental displacement trajectories, obtained on flat two-dimensional surfaces, have been analyzed using advanced non-linear quantitative approaches. Our results show that both non-enucleated amoebas and cytoplasts display the same complex kind of dynamic structure in their migratory trajectories. The locomotion displacements of enucleated cells are regulated by complex self-organized integrative dynamics, modulated at a global-systemic level which seems to depend on the cooperative interaction of most, if not all, molecular components of cells.

systems biology↗

bioRxiv2024

Forces directing the systemic correlations of cell migration

Directional motility is an essential property of cells. Despite its enormous relevance in many fundamental physiological and pathological processes, how cells control their locomotion movements remains an unresolved question. Here we have addressed the systemic processes driving the directed locomotion of cells. Specifically, we have performed an exhaustive study analyzing the trajectories of 700 individual cells belonging to three different species (Amoeba proteus, Metamoeba leningradensis and Amoeba borokensis) in four different scenarios: in absence of stimuli, under an electric field (galvanotaxis), in a chemotactic gradient (chemotaxis), and under simultaneous galvanotactic and chemotactic stimuli. All movements were analyzed using advanced quantitative tools. The results show that the trajectories are mainly characterized by coherent integrative responses that operate at the global cellular scale. These systemic migratory movements depend on the cooperative non-linear interaction of most, if not all, molecular components of cells. SignificanceCellular migration is a cornerstone issue in many human physiological and pathological processes. For years, the scientific attention has been focused on the individualized study of the diverse molecular parts involved in directional motility; however, locomotion movements have never been regarded as a systemic process that operates at a global cellular scale. In our quantitative experimental analysis essential systemic properties underlying locomotion movements were detected. Such emergent systemic properties are not found specifically in any of the molecular parts, partial mechanisms, or individual processes of the cell. Cellular displacements seem to be regulated by integrative processes operating at systemic level.

systems biology↗

bioRxiv2018

Evidences of conditioned behavior in Amoeba proteus

Associative memory is the main type of learning wherein complex organisms endowed with evolved nervous systems respond efficiently to determined environmental stimuli. This fundamental cognitive property has been evidenced in different multicellular species, from cephalopods to Humans, but never in individual cells. Here, following Pavlovs experiments with dogs that founded the principles of classical conditioning, we have observed the development of an associative memory in Amoeba proteus, which corresponds to the emergence of a new systemic motility pattern. In our cellular version of this conditioning behavior, we have used a controlled direct current electric field as the conditioned stimulus and a specific chemotactic peptide as the non-conditioned stimulus. Our study allowed us to demonstrate that Amoeba proteus are capable of linking two independent past events, and the induced associative memory can be recorded for up to at least four hours. For the first time, it has been observed that a systemic response to a specific stimulus can be modified by learning in unicellular organisms. This finding opens up a new framework in the understanding of the mechanisms underlying the complex systemic behavior involved in the cellular migration and the adaptive capacity of cells to the external medium.

systems biology↗