Cell-size distribution in epithelial tissue formation and homeostasis.
How cell growth and proliferation are orchestrated in living tissues to achieve a given biological function is a central problem in biology. During development, tissue regeneration and homeostasis, cell proliferation must be coordinated by spatial cues in order for cells to attain the correct size and shape. Biological tissues also feature a notable homogeneity of cell size, which, in specific cases, represents a physiological need. Here, we study the temporal evolution of the cell-size distribution by applying the theory of kinetic fragmentation to tissue development and homeostasis. Our theory predicts self-similar probability density function (PDF) of cell size and explains how division times and redistribution ensure cell size homogeneity across the tissue. Theoretical predictions and numerical simulations of confluent non-homeostatic tissue cultures show that cell size distribution is self-similar. Our experimental data confirm predictions and reveal that, as assumed in the theory, cell division times scale like a power-law of the cell size. We find that in homeostatic conditions there is a stationary distribution with lognormal tails, consistently with our experimental data. Our theoretical predictions and numerical simulations show that the shape of the PDF depends on how the space inherited by apoptotic cells is redistributed and that apoptotic cell rates might also depend on size.
Candiolo Cancer Institute FPO-IRCCS, Candiolo, Turin, Italy alberto.puliafito@ircc.it.
Alberto
0000-0002-0096-1536
A
Puliafito
Candiolo Cancer Institute FPO-IRCCS, Candiolo, Turin, Italy.|Department of Oncology, University of Turin, Turin 10060, Italy.
Luca
L
Primo
Quantitative Life Sciences Unit, The Abdus Salam Center for Theoretical Physics (ICTP), Strada Costiera 11, 34151 Trieste, Italy.
Antonio
A
Celani
D000818:Animals; D002455:Cell Division; D048429:Cell Size; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006706:Homeostasis; D061985:Madin Darby Canine Kidney Cells; D008954:Models, Biological
epithelial tissues; growth regulation; master equation; theories of collective dynamics