Stem cell self-renewal: The role of asymmetric division

Terskikh, V. V.; Vasil’ev, A. V.; Воротеляк, Е. А.

doi:10.1134/s106235900905001x

Cited by 2 publications

(1 citation statement)

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“…Protein aggregates, dysfunction organelles and DNA damage are commonly identified as factors of ageing [4,5]. To slow down the accumulation of ageing factors, a hypothesis suggests that mitotic cells (actively dividing cells) might asymmetrically segregate damage away from the cell whose fate is to become a new stem cell [8]. The asymmetric inheritance of cellular components in dividing cells was first observed in yeast, and has been extensively studied over the past decades.…”

Section: Introductionmentioning

confidence: 99%

Modelling stem cell ageing: a multi-compartment continuum approach

Wang

Chou

2020

R. Soc. open sci.

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Stem cells are important to generate all specialized tissues at an early life stage, and in some systems, they also have repair functions to replenish the adult tissues. Repeated cell divisions lead to the accumulation of molecular damage in stem cells, which are commonly recognized as drivers of ageing. In this paper, a novel model is proposed to integrate stem cell proliferation and differentiation with damage accumulation in the stem cell ageing process. A system of two structured PDEs is used to model the population densities of stem cells (including all multiple progenitors) and terminally differentiated (TD) cells. In this system, cell cycle progression and damage accumulation are modelled by continuous dynamics, and damage segregation between daughter cells is considered at each division. Analysis and numerical simulations are conducted to study the steady-state populations and stem cell damage distributions under different damage segregation strategies. Our simulations suggest that equal distribution of the damaging substance between stem cells in a symmetric renewal and less damage retention in stem cells in the asymmetric division are favourable strategies, which reduce the death rate of the stem cells and increase the TD cell populations. Moreover, asymmetric damage segregation in stem cells leads to less concentrated damage distribution in the stem cell population, which may be more robust to the stochastic changes in the damage. The feedback regulation from stem cells can reduce oscillations and population overshoot in the process, and improve the fitness of stem cells by increasing the percentage of cells with less damage in the stem cell population.

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Section: Introductionmentioning

confidence: 99%