title: Mathematical modeling of growth and death dynamics of mouse embryonic stem cells irradiated with γ-rays.
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.
authors.affiliation: Dipartimento di Ingegneria Industriale e dell׳Informazione, Università degli Studi di Pavia, Via Ferrata 5, I-27100 Pavia, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Terranova
authors.affiliation: Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", Università degli Studi di Pavia, Via Ferrata 9, I-27100 Pavia, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Rebuzzini
authors.affiliation: Sezione di Istochimica e Citometria, Istituto di Genetica Molecolare CNR, Via Ferrata 9, I-27100 Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mazzini
authors.affiliation: Dipartimento di Ingegneria Industriale e dell׳Informazione, Università degli Studi di Pavia, Via Ferrata 5, I-27100 Pavia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Borella
authors.affiliation: Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", Università degli Studi di Pavia, Via Ferrata 9, I-27100 Pavia, Italy; Fondazione I.R.C.C.S. Policlinico San Matteo, Piazzale Golgi, Pavia, Italy.
authors.forename: C A
authors.initials: CA
authors.lastname: Redi
authors.affiliation: Unità di Anatomia, Istologia ed Embriologia, Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali (S.Bi.Bi.T.), Università degli Studi di Parma, Via Volturno 39, I-43100 Parma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zuccotti
authors.affiliation: Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", Università degli Studi di Pavia, Via Ferrata 9, I-27100 Pavia, Italy; Centro di Ingegneria Tissutale (C.I.T), Università degli Studi di Pavia, Via Ferrata 5, I-27100 Pavia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Garagna
authors.affiliation: Dipartimento di Ingegneria Industriale e dell׳Informazione, Università degli Studi di Pavia, Via Ferrata 5, I-27100 Pavia, Italy; Centro di Ingegneria Tissutale (C.I.T), Università degli Studi di Pavia, Via Ferrata 5, I-27100 Pavia, Italy. Electronic address: paolo.magni@unipv.it.
authors.forename: P
authors.initials: P
authors.lastname: Magni
mesh_terms: D000818:Animals; D017304:Annexin A5; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D053595:Embryonic Stem Cells / Q000502:physiology* / Q000528:radiation effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000502:physiology* / Q000528:radiation effects; D005720:Gamma Rays; D051379:Mice; D008954:Models, Biological; D013997:Time Factors
chemical_list: D017304:Annexin A5
keywords: Cell death; Cell growth; Ionizing irradiation