title: Stretched cell cycle model for proliferating lymphocytes.
abstract: Stochastic variation in cell cycle time is a consistent feature of otherwise similar cells within a growing population. Classic studies concluded that the bulk of the variation occurs in the G1 phase, and many mathematical models assume a constant time for traversing the S/G2/M phases. By direct observation of transgenic fluorescent fusion proteins that report the onset of S phase, we establish that dividing B and T lymphocytes spend a near-fixed proportion of total division time in S/G2/M phases, and this proportion is correlated between sibling cells. This result is inconsistent with models that assume independent times for consecutive phases. Instead, we propose a stretching model for dividing lymphocytes where all parts of the cell cycle are proportional to total division time. Data fitting based on a stretched cell cycle model can significantly improve estimates of cell cycle parameters drawn from DNA labeling data used to monitor immune cell dynamics.
authors.affiliation: Division of Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Dowling
authors.forename: Andrey
authors.initials: A
authors.lastname: Kan
authors.forename: Susanne
authors.initials: S
authors.lastname: Heinzel
authors.forename: Jie H S
authors.initials: JH
authors.lastname: Zhou
authors.forename: Julia M
authors.initials: JM
authors.lastname: Marchingo
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Wellard
authors.forename: John F
authors.initials: JF
authors.lastname: Markham
authors.forename: Philip D
authors.initials: PD
authors.lastname: Hodgkin
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D005453:Fluorescence; D017930:Genes, Reporter; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D011336:Probability; D013601:T-Lymphocytes / Q000166:cytology*; D013997:Time Factors
chemical_list: D004247:DNA; D001973:Bromodeoxyuridine
keywords: FUCCI; Smith-Martin model; bromodeoxyuridine; lognormal distribution; time lapse microscopy
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