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A G1 Sizer Coordinates Growth and Division in the Mouse Epidermis

2020; Elsevier BV; Volume: 30; Issue: 5 Linguagem: Inglês

10.1016/j.cub.2019.12.062

1879-0445

Shicong Xie, Jan M. Skotheim,

Plant Molecular Biology Research

Cell size homeostasis is often achieved by coupling cell-cycle progression to cell growth. Growth has been shown to drive cell-cycle progression in bacteria and yeast through “sizers,” wherein cells of varying birth size divide at similar final sizes [1Di Talia S. Skotheim J.M. Bean J.M. Siggia E.D. Cross F.R. The effects of molecular noise and size control on variability in the budding yeast cell cycle.Nature. 2007; 448: 947-951Crossref PubMed Scopus (321) Google Scholar, 2Sveiczer A. Novak B. Mitchison J.M. The size control of fission yeast revisited.J. Cell Sci. 1996; 109: 2947-2957PubMed Google Scholar, 3Schmoller K.M. Turner J.J. Kõivomägi M. Skotheim J.M. Dilution of the cell cycle inhibitor Whi5 controls budding-yeast cell size.Nature. 2015; 526: 268-272Crossref PubMed Scopus (142) Google Scholar], and “adders,” wherein cells increase in size a fixed amount per cell cycle [4Taheri-Araghi S. Bradde S. Sauls J.T. Hill N.S. Levin P.A. Paulsson J. Vergassola M. Jun S. Cell-size control and homeostasis in bacteria.Curr. Biol. 2015; 25: 385-391Abstract Full Text Full Text PDF PubMed Scopus (348) Google Scholar, 5Campos M. Surovtsev I.V. Kato S. Paintdakhi A. Beltran B. Ebmeier S.E. Jacobs-Wagner C. A constant size extension drives bacterial cell size homeostasis.Cell. 2014; 159: 1433-1446Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar, 6Soifer I. Robert L. Amir A. Single-cell analysis of growth in budding yeast and bacteria reveals a common size regulation strategy.Curr. Biol. 2016; 26: 356-361Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar]. Intermediate control phenomena are also observed, and even the same organism can exhibit different control phenomena depending on growth conditions [2Sveiczer A. Novak B. Mitchison J.M. The size control of fission yeast revisited.J. Cell Sci. 1996; 109: 2947-2957PubMed Google Scholar, 7Wallden M. Fange D. Lundius E.G. Baltekin Ö. Elf J. The synchronization of replication and division cycles in individual E. coli cells.Cell. 2016; 166: 729-739Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar, 8Delarue M. Weissman D. Hallatschek O. A simple molecular mechanism explains multiple patterns of cell-size regulation.PLoS ONE. 2017; 12: e0182633Crossref PubMed Scopus (12) Google Scholar]. Although studying unicellular organisms in laboratory conditions may give insight into their growth control in the wild, this is less apparent for studies of mammalian cells growing outside the organism. Sizers, adders, and intermediate phenomena have been observed in vitro [9Ginzberg M.B. Chang N. D’Souza H. Patel N. Kafri R. Kirschner M.W. Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity.eLife. 2018; 7: 7729Crossref Scopus (41) Google Scholar, 10Cadart C. Monnier S. Grilli J. Sáez P.J. Srivastava N. Attia R. Terriac E. Baum B. Cosentino-Lagomarsino M. Piel M. Size control in mammalian cells involves modulation of both growth rate and cell cycle duration.Nat. Commun. 2018; 9: 3275Crossref PubMed Scopus (67) Google Scholar, 11Varsano G. Wang Y. Wu M. Probing mammalian cell size homeostasis by channel-assisted cell reshaping.Cell Rep. 2017; 20: 397-410Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 12Berenson D.F. Zatulovskiy E. Xie S. Skotheim J.M. Constitutive expression of a fluorescent protein reports the size of live human cells.Mol. Biol. Cell. 2019; 30: 2985-2995Crossref PubMed Scopus (5) Google Scholar], but it is unclear how this relates to mammalian cell proliferation in vivo. To address this question, we analyzed time-lapse images of the mouse epidermis taken over 1 week during normal tissue turnover [13Mesa K.R. Kawaguchi K. Cockburn K. Gonzalez D. Boucher J. Xin T. Klein A.M. Greco V. Homeostatic epidermal stem cell self-renewal is driven by local differentiation.Cell Stem Cell. 2018; 23: 677-686.e4Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. We quantified the 3D volume growth and cell-cycle progression of single cells within the mouse skin. In dividing epidermal stem cells, we found that cell growth is coupled to division through a sizer operating largely in the G1 phase of the cell cycle. Thus, although the majority of tissue culture studies have identified adders, our analysis demonstrates that sizers are important in vivo and highlights the need to determine their underlying molecular origin.