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Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress
Published on: May 7, 2014
Mathematical modeling of growth and death dynamics of mouse embryonic stem cells irradiated with γ-rays
N Terranova1, P Rebuzzini2, G Mazzini3
1Dipartimento di Ingegneria Industriale e dell׳Informazione, Università degli Studi di Pavia, Via Ferrata 5, I-27100 Pavia, Italy.
Abstract:
Following ionizing radiation, mouse embryonic stem cells (mESCs) undergo both apoptosis and block at G2/M phase of the cell cycle. The dynamics of cell growth and the transition through the apoptotic phases cannot be directly inferred from experimental data, limiting the understanding of the biological response to the treatment. Here, we propose a semi-mechanistic mathematical model, defined by five compartments, able to describe the time curves of untreated and γ-rays irradiated mESCs and to extract the information therein embedded. To this end, mESCs were irradiated with 2 or 5 Gy γ-rays, collected over a period of 48 h and, at each time point, analyzed for apoptosis by using the Annexin V assay. When compared to unirradiated mESCs, the model estimates an additional 0.2 probability to undergo apoptosis for the 5 Gy-treated cells, and only a 0.07 (not statistically significantly different from zero) when a 2 Gy-irradiation dose is administered. Moreover, the model allows us to estimate the duration of the overall apoptotic process and also the time length of its early, intermediate, and late apoptotic phase.
Insights
Ionizing radiation induces apoptosis and cell cycle arrest in mouse embryonic stem cells (mESCs). A new mathematical model quantifies radiation-induced apoptosis probability and its phase durations in mESCs.
Area of Science:
- Cell Biology
- Radiation Biology
- Mathematical Modeling
Background:
- Ionizing radiation exposure triggers apoptosis and G2/M cell cycle arrest in mouse embryonic stem cells (mESCs).
- Understanding the precise dynamics of mESC response, including apoptosis progression, is crucial but challenging due to limitations in directly interpreting experimental data.
- Existing methods struggle to capture the temporal nuances of cell death pathways following radiation treatment.
Purpose of the Study:
- To develop and validate a semi-mechanistic mathematical model to describe the time-dependent behavior of mESCs after ionizing radiation exposure.
- To quantify the probability of apoptosis induction in mESCs at different radiation doses (2 Gy and 5 Gy).
- To estimate the temporal parameters of the apoptotic process, including overall duration and individual phase lengths.
Main Methods:
- Mouse embryonic stem cells (mESCs) were irradiated with 2 Gy or 5 Gy of gamma rays.
- Cell samples were collected over 48 hours post-irradiation.
- Apoptosis was quantified using the Annexin V assay at each time point.
- A five-compartment semi-mechanistic mathematical model was developed to analyze the time-course data.
Main Results:
- The mathematical model successfully described the time curves of both untreated and irradiated mESCs.
- A 5 Gy dose significantly increased the probability of apoptosis by an estimated 0.2 compared to controls.
- A 2 Gy dose resulted in a non-statistically significant increase in apoptosis probability (0.07).
- The model provided estimations for the duration of the entire apoptotic process and its distinct early, intermediate, and late phases.
Conclusions:
- The developed mathematical model offers a robust framework for analyzing mESC responses to ionizing radiation.
- The model quantitatively differentiates the apoptotic potential of varying radiation doses.
- This approach enhances the understanding of radiation-induced cell death dynamics in stem cells, aiding in radiobiology research.
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