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1/8
There have been many helpful analogies for understanding the cell cycle—oscillator, clock, dominoes—but what if we could actually *see* the cell cycle as a complete process? What would it look like?
The structure of the human cell cycle https://www.biorxiv.org/content/10.1101/2021.02.11.430845v1
There have been many helpful analogies for understanding the cell cycle—oscillator, clock, dominoes—but what if we could actually *see* the cell cycle as a complete process? What would it look like?
The structure of the human cell cycle https://www.biorxiv.org/content/10.1101/2021.02.11.430845v1
2/8
A team led by @WStallaert combined time-lapse microscopy, multiplexed single-cell imaging , and manifold learning to get a glimpse of the underlying “structure” of the human cell cycle. Here is the picture that emerged:
A team led by @WStallaert combined time-lapse microscopy, multiplexed single-cell imaging , and manifold learning to get a glimpse of the underlying “structure” of the human cell cycle. Here is the picture that emerged:
3/8
This trident-like structure shows cells exiting mitosis down a central arm and proceeding toward either proliferation (right arm) or arrest (left arm).
This trident-like structure shows cells exiting mitosis down a central arm and proceeding toward either proliferation (right arm) or arrest (left arm).
4/8
Cells traveling down the proliferative arm showed expected changes in DNA content, cell size, E2F1, cyclin D, cyclin E, Cdh1, cyclin A, PCNA foci, and dozens of other core cell cycle regulators:
Cells traveling down the proliferative arm showed expected changes in DNA content, cell size, E2F1, cyclin D, cyclin E, Cdh1, cyclin A, PCNA foci, and dozens of other core cell cycle regulators:
5/8
So far, so good. But what about the arrest arm? Here’s where things got interesting. As cells went deeper into arrest, they accumulated more p21, p53, and p16, as expected. However, they also accumulated more *proliferative* factors like cyclin E, cyclin D1, and CDK4.
So far, so good. But what about the arrest arm? Here’s where things got interesting. As cells went deeper into arrest, they accumulated more p21, p53, and p16, as expected. However, they also accumulated more *proliferative* factors like cyclin E, cyclin D1, and CDK4.
6/8
At some point, these proliferative factors overwhelm the arrest factors, sending cells back into the proliferative cell cycle—along a different route! We know this because live-imaging shows cells reactivating CDK activity hours before losing p21 expression.
At some point, these proliferative factors overwhelm the arrest factors, sending cells back into the proliferative cell cycle—along a different route! We know this because live-imaging shows cells reactivating CDK activity hours before losing p21 expression.
7/8
Perturbing the cell cycle with various stresses revealed additional trajectories toward senescence, endoreduplication, and polyploidy. This complex web of molecular states show the remarkable plasticity underlying one of the cell’s most fundamental processes.
Perturbing the cell cycle with various stresses revealed additional trajectories toward senescence, endoreduplication, and polyploidy. This complex web of molecular states show the remarkable plasticity underlying one of the cell’s most fundamental processes.
8/8
Thanks to the superb team of scientists, @WStallaert @KateKedziora, Colin Taylor, @tarekmzikry, Holly Sobon, Sophie Taylor, Catherine Young, @proud_rpcv, and @dnatarheel. This work was inspired and enabled by prior work from @lucaspelkmans, @dana_peer, and @KrishnaswamyLab.
Thanks to the superb team of scientists, @WStallaert @KateKedziora, Colin Taylor, @tarekmzikry, Holly Sobon, Sophie Taylor, Catherine Young, @proud_rpcv, and @dnatarheel. This work was inspired and enabled by prior work from @lucaspelkmans, @dana_peer, and @KrishnaswamyLab.
