Abstract
In multi-cellular organisms, tissue homeostasis is maintained by an exquisite balance between stem cell proliferation and differentiation. This equilibrium can be achieved either at the single cell level (a.k.a. cell asymmetry), where stem cells follow strict asymmetric divisions, or the population level (a.k.a. population asymmetry), where gains and losses in individual stem cell lineages are randomly distributed, but the net effect is homeostasis. In the mature mouse intestinal crypt, previous evidence has revealed a pattern of population asymmetry through predominantly symmetric divisions of stem cells. In this work, using population genetic theory together with previously published crypt single-cell data obtained at different mouse life stages, we reveal a strikingly dynamic pattern of stem cell homeostatic control. We find that single-cell asymmetric divisions are gradually replaced by stochastic population-level asymmetry as the mouse matures to adulthood. This lifelong process has important developmental and evolutionary implications in understanding how adult tissues maintain their homeostasis integrating the trade-off between intrinsic and extrinsic regulations.
Highlights
Development and tissue homeostasis of multi-cellular organisms is an extraordinary cellular orchestra starting from a single zygote [1]
Using population genetic theory together with previously published single-cell sequencing data collected from mouse intestinal crypts at two points in development, we have revealed a dynamic picture of stem cell renewal in intestinal crypts
We found that intestinal equilibrium is maintained at the single-cell level through predominantly asymmetric stem cell divisions at early life stages, but progressively switches to a population level homeostasis with only symmetric divisions as the mouse matures to adulthood
Summary
Development and tissue homeostasis of multi-cellular organisms is an extraordinary cellular orchestra starting from a single zygote [1]. Cascades of cell divisions generate and subsequently maintain a great diversity of cells in an organism [2]. This life-long balance is strictly controlled and maintained through a rigid cellular hierarchy, where the stem cells lie at the apex of the division cascades [3]. Stem cells are a group of cells with a dual role. On one hand, they need to maintain their own population through self-renewal. In order to fulfill the dual role of self-renewal and differentiation, stem cells can undergo two different modes of cell division – asymmetric and symmetric [5]. The stem cells can divide symmetrically, leading to either two stem cells or two differentiated cells
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