New study finds link between cell division and growth rate

In simple organisms such as yeast, cells divide once they reach a specific size. However, determining if this holds true for mammalian cells has been difficult, in part because there has been no good way to measure mammalian cell growth over time. Now, a team of MIT and Harvard Medical School (HMS) researchers has precisely measured the growth rates of single cells, allowing them to answer that fundamental question. In the Aug. 5 online edition of Nature Methods, the researchers report that mammalian cells divide not when they reach a critical size, but when their growth rate hits a specific threshold.




This first-ever observation of this threshold was made possible by a technique developed by MIT professor Scott Manalis and his students in 2007 to measure the mass of single cells. In the new study, Manalis and his colleagues were able to track cell growth and relate it to the timing of cell division by measuring cells’ mass every 60 seconds throughout their lifespans.

The finding offers a possible explanation for how cells determine when to start dividing, says Sungmin Son, a grad student in Manalis’ lab and lead author of the paper. “It’s easier for cells to measure their growth rate, because they can do that by measuring how fast something in the cell is produced or degraded, whereas measuring size precisely is hard for cells,” Son says.

Manalis, a professor of biological engineering and member of the David H. Koch Institute for Integrative Cancer Research at MIT, is senior author of the paper. Other authors are former MIT grad student Yaochung Weng; Amit Tzur, a former research fellow at HMS; Paul Jorgensen, a former HMS postdoc; Jisoo Kim, a former undergraduate student at MIT; and Marc Kirschner, a professor of systems biology at HMS.The new system also measures fluorescent signals from a cell in addition to its mass. Cells are programmed to express fluorescent proteins at various points in the cell cycle, allowing the researchers to link cell cycle information to growth.

A cell devotes itself to growth in a phase called G1. A critical transition occurs when the cell enters the S phase, during which DNA is replicated in preparation for division. The researchers found that growth rate increases rapidly during the G1 phase. This rate varies a great deal from cell to cell during G1, but converges as cells approach the S phase. Once cells complete the transition into S phase, growth rates diverge again.“We are now measuring the cell’s response on short timescales to various perturbations, such as depleting a particular nutrient or adding a drug,” Manalis says. “We believe this could offer new types of information that could not be obtained from conventional proliferation assays.”

“It’s very exciting that they can now make these supersensitive measurements and quantify how growth changes in response to therapeutic interventions,” says Dean Felsher, an associate professor of medicine at Stanford Medical School, who was not part of this study. “Being able to measure growth at the individual cell level will help in the hunt for genes that regulate growth and for drugs that have preclinical activity.”

#CellCycle #CellGrowth #Interphase #Prophase #Metaphase #Anaphase #Telophase #Cytokinesis #Mitosis #G1Phase #SPhase #G2Phase #Checkpoints #CDK #Cyclins #CellBiology #CellCycleRegulation

#CellDivision #Mitosis #Meiosis #Chromosomes #Chromatids #SpindleFibers #Centromeres #Centrosomes #DNAReplication #GeneticMaterial #CellularReproduction #SomaticCells #GermCells #CellDivisionStages #Biology #LifeSciences

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