Biology subjects

Eidelman, Y.

Publications and source records attributed to Eidelman, Y..

10 recordsLinked to original sources

bioRxiv2025

Analysis of the possible pathways of cancer cell repopulation after irradiation in vitro

The study of the pathways of cancer stem cell (CSC) repopulation after therapeutic exposure is of great importance for planning effective therapy schemes. In this work, a mathematical model of the proliferation of a population of cancer cells after irradiation is developed, taking into account the presence of three subpopulations (differentiated cancer cells, CSCs, and senescent cells), the plasticity of malignant cells (dedifferentiation, transition of non-stem cells to a stem state), and the transition of cells to a senescent state following irradiation. It is shown that the phenomenon of an increase in the fraction of CSCs after irradiation, observed in the in vitro experiment on MCF-7 breast cancer cells, can be explained by symmetrical division of CSCs and dedifferentiation of non-stem cancer cells.

cancer biology↗

bioRxiv2019

Spatial organization of the mouse chromosomes influences the landscape of intrachromosomal exchange aberration breakpoints

How 3D chromosome organization affects chromosomal aberrations is an important unresolved question in cell and radiation biology. In interphase the chromosomes form territories where chromatin folds into quite heterogeneous states. The mechanisms determining the spectrum of chromosome conformations remain poorly understood. We introduced the polymer model of mouse chromosome and generated the ensemble of 3D conformations. The chromosome model was validated against independent Hi-C (high-throughput chromosome conformation capture) data. The model described well Hi-C contact heatmap for chromosome 18 in pro-B mouse cells, both ATM-deficient and wild-type. We used the chromosome model to assess the role of chromosome structure in breakpoint distribution for intrachromosomal exchange aberrations. We investigated the effect of elevated frequency of breakpoints outside of the region of enzymatic breaksite. Chromosome aberration model explained breakpoint distribution under recurrent and ionizing radiation-induced DNA double-strand breaks in mouse chromosome 18 on the basis of contact-first mechanism. Overall, our results provide a framework for assessment of role of chromosome 3D organization on chromosome aberrations following DNA damage of different origin.

cancer biology↗

bioRxiv2018

Chromosome compartmentalization replacement during stem cell differentiation

In this paper, changes in a large-scale 3D structure of chromosomes during stem cell differentiation is studied. The polymer coarse-grained model of a human interphase chromosome is introduced which reproduces the experimental Hi-C contact maps in chromosomes 12, 17 for both embryonic stem and differentiated cells with high accuracy. Model based analysis of Hi-C data suggests a mechanism of establishment of preferential long-range chromosomal contacts and compartmentalization replacement during cell stem differentiation. The model provides the conceptual basis for integration of data on the dynamics of chromatin interactions, the 3D structure of chromosomes and gene expression during stem cell differentiation or reprogramming.

biophysics↗

bioRxiv2017

Dose response relationships for gamma radiation induced chromosomal instability

Different cell lines demonstrate various dose response for radiation-induced chromosomal instability (RICI). To clarify the origin of differences we analyzed own and published data on RICI for four cell lines, V79, TK6, WTK1 and CHO-K1 on the basis of the mechanistic RICI model. We conclude that observable dose-response shapes, both plateau-like and strong dose dependent behavior, may be jointly explained by the same model of RICI. Mechanistic modeling reveals that a variation of certain set of RICI parameters leads to strong modification of dose-response curve.

cancer biology↗

bioRxiv2017

Quantifying relationships between chromosome organization and chromosomal aberrations

The question of to what extent large scale structure of interphase chromosomes contributes to chromosomal exchange aberrations is discussed for a long time but still remains unclear. We designed the polymer model of 3D organization of a mouse chromosome and simulated X-ray induced chromosomal aberrations exploring two alternative hypotheses: the probability of contacted damaged loci entailing a chromosomal rearrangement is (a) a constant value or (b) not constant, depending on the distribution of DNAsel-hypersensitivity peaks along the chromosome. The latter hypothesis proved to explain the experimental data better than the former, meaning that not only large-scale structure but also local chromatin alterations play a role.

systems biology↗

bioRxiv2017

Quantitative relationships for radiation induced chromosome instability: data analysis

The experimental observations demonstrate that different cell lines reveal various shape of dynamic curves for radiation-induced chromosomal instability (RICI). We analyzed our own and published data on RICI for three cell lines, CHO-K1, V79 and TK6, on the basis of the mechanistic RICI model. We demonstrate that all three dynamic curves can be successfully described by the proposed model with partially cell line specific parameters.

cancer biology↗

bioRxiv2017

DNA Damage Induced Chromosomal Instability. Computational modeling view.

The origin of dose-response curves for radiation-induced chromosomal instability (CI) is studied using the mechanistic CI model. The model takes into account DNA damage generation and repair in the progeny of irradiated cells, cell passage through mitotic cycle, and intercellular signaling. It is shown that the dose-response curves are closely related to the dynamic curves. The principles underlying this relationship are analyzed.

systems biology↗

bioRxiv2016

Relationships between chromosomal aberration breakpoints and chromosomal contacts: biophysical modeling study

Radiation-induced chromosomal exchange aberrations (CAs) are formed presumably at contacts of damaged chromosomal loci. For sparsely ionizing radiation, distribution of aberrations along the chromosome should depend on distribution of contacts, i.e. on 3D organization of the chromosome. The progress in experimental techniques for study of chromosomal contacts and for precise localization of aberration breakpoints allows to verify contacts-based mechanisms of CA formation experimentally. In the present work, the polymer model of mouse interphase chromosome 18 is developed. On this basis the experimental data on contacts and aberrations are jointly analyzed. We demonstrate high correlation between chromosomal contacts and aberrations breakpoint distributions. Possible factors and alternative mechanisms which could modify breakpoint distributions are discussed.

cancer biology↗

bioRxiv2016

Physical models of spatial genome organization

Remodeling of nuclear organization occurs during normal cell development, differentiation and cancer. One of the biggest gaps of knowledge remains how to link the information on chromatin and chromosome structural organization with genes activity. In this paper we introduce some physical ideas and a general computational method demonstrating how genome 3D architecture and its remodeling can be quantitatively modeled. We study a hypothetical scenario of alterations of chromosome territories positioning in the course of cell proliferation. On this basis we obtain quantitative information about chromosomal contacts in the nucleus. We predict changes of radial distributions of contacts between chromosomal megabase domains during proliferation. The proposed modeling approach may be helpful in integrating experimental data on nuclear reorganization associated with normal development and with various diseases. This predictive modeling may find applications in genome research of normal and cancer cells, stem cell biology, biology of aging, etc.

cancer biology↗

bioRxiv2016

Chromosome interactome inferred from mitosis-G1 transition

The progress in experimental techniques aimed at 3D genome study is yet to bring about revelation of basic principles of genome folding. Chromosome conformation capture Hi-C technologies provide genome wide mapping of genomic loci interactions but spatial organization of chromosomes remains unknown. Here, we develop a polymer modeling approach to generate the ensemble of 3D chromosome conformations for mapping genetic loci contacts and the positions of megabase chromosomal domains in interphase chromosome at different time of mitosis-interphase transition. We demonstrate that (*) whole chromosome contact map (interactome) generated for mouse chromosome 18 structure and (**) contact patterns, observed soon after mitotic decondensation and remaining similar during G1, correlate well with the experimental Hi-C contact data. The results suggest that contact map formation and spatial compartmentalization of an interphase chromosome are driven by interactions between different types of domains during formation of globular chromosome state at the end of mitotis-G1 transition.

biophysics↗