Abstract
In multicellular organisms one can find examples where a growing tissue divides up until some final fixed cell number. Asymmetric division plays a prevalent feature in tissue differentiation in these organisms, where the daughters of each asymmetric division inherit unequal amounts of a fate determining molecule and as a result follow different developmental fates. In some tissues the accumulation or decrease of cell cycle regulators acts as an intrinsic timing mechanism governing proliferation. Here we present a minimal model based on asymmetric division and dilution of a cell-cycle regulator that can generate any final population size that might be needed. We show that within the model there are a variety of growth mechanisms from linear to non-linear that can lead to the same final cell count. Interestingly, when we include noise at division we find that there are special final cell population sizes that can be generated with high confidence that are flanked by population sizes that are less robust to division noise. When we include further perturbations in the division process we find that these special populations can remain relatively stable and in some cases even improve in their fidelity.
Highlights
There are multiple examples of cell populations with controlled final numbers
Deterministic Cell Division and Partitioning Using our model we explored whether asymmetric division coupled with dilution of a regulatory molecule could generate an arbitrary final cell count
In this paper we have shown how an hourglass model for an intrinsic cell cycle factor coupled with asymmetric division can produce an arbitrary final cell population size
Summary
There are multiple examples of cell populations with controlled final numbers. The size and the accuracy with which this final population number is reached vary. In the proliferation and differentiation of tissue, both extrinsic and intrinsic cues have been found to play critical roles in robust size control of the cell population [2,4,5]. Purely intrinsic or autonomous cues play a role as a variety of cultured or transplanted stem cells can produce lineages nearly identical to those in the endogenous locations. These intrinsic timers have been shown to arise from temporal cascades of transcription factors (as in many neuroblasts [3,6]) to the accumulation of cell cycle regulators in oligodendrocytes [7,8]. As cells divide an internal molecular clock akin to an hourglass dictates when they should exit the cell cycle and enter a quiescent stage [8]
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