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Age-dependent transition from cell-level to population-level control in murine intestinal homeostasis revealed by coalescence analysis.

Hu Z, Fu YX, Greenberg AJ, Wu CI, Zhai W - PLoS Genet. (2013)

Bottom Line: 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 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Computational Biology and Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.

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.

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Lifelong equilibrium for stem cell symmetric/asymmetric divisions.(A) The proportion of asymmetric and symmetric division as a function of mouse life stage. The pattern from morphogenesis are from experimental data together with the optimal control theory prediction [25]. The lineage tracing evidences are from two earlier studies [23], [24]. The transition from cell asymmetry to population asymmetry can take a variety of forms, including I) a fast switch similar to the Bang-Bang control, II) a linear accumulation, III) slow progression depending on the interplay between intrinsic and extrinsic signals. (B) When simulating crypt histories using curve I, II and III in Figure 3A and plotting mean pairwise divergence time between two random cells (a measurement of genealogical length), the average pairwise divergence shows very different trajectories under different transitional history.
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pgen-1003326-g003: Lifelong equilibrium for stem cell symmetric/asymmetric divisions.(A) The proportion of asymmetric and symmetric division as a function of mouse life stage. The pattern from morphogenesis are from experimental data together with the optimal control theory prediction [25]. The lineage tracing evidences are from two earlier studies [23], [24]. The transition from cell asymmetry to population asymmetry can take a variety of forms, including I) a fast switch similar to the Bang-Bang control, II) a linear accumulation, III) slow progression depending on the interplay between intrinsic and extrinsic signals. (B) When simulating crypt histories using curve I, II and III in Figure 3A and plotting mean pairwise divergence time between two random cells (a measurement of genealogical length), the average pairwise divergence shows very different trajectories under different transitional history.

Mentions: Previous observations revealed that mouse crypt morphogenesis started with a surge of symmetric divisions establishing the pool of stem cells, followed by a transition to predominantly asymmetric divisions that maintain an equilibrium between stem cell self-renewal and differentiation [25]. Our results support the existence of a second transition from mostly asymmetric stem cell divisions to symmetric divisions during intestinal homeostasis (Figure 3A). It remains to be seen whether this phenomenon also occurs in other systems.


Age-dependent transition from cell-level to population-level control in murine intestinal homeostasis revealed by coalescence analysis.

Hu Z, Fu YX, Greenberg AJ, Wu CI, Zhai W - PLoS Genet. (2013)

Lifelong equilibrium for stem cell symmetric/asymmetric divisions.(A) The proportion of asymmetric and symmetric division as a function of mouse life stage. The pattern from morphogenesis are from experimental data together with the optimal control theory prediction [25]. The lineage tracing evidences are from two earlier studies [23], [24]. The transition from cell asymmetry to population asymmetry can take a variety of forms, including I) a fast switch similar to the Bang-Bang control, II) a linear accumulation, III) slow progression depending on the interplay between intrinsic and extrinsic signals. (B) When simulating crypt histories using curve I, II and III in Figure 3A and plotting mean pairwise divergence time between two random cells (a measurement of genealogical length), the average pairwise divergence shows very different trajectories under different transitional history.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585040&req=5

pgen-1003326-g003: Lifelong equilibrium for stem cell symmetric/asymmetric divisions.(A) The proportion of asymmetric and symmetric division as a function of mouse life stage. The pattern from morphogenesis are from experimental data together with the optimal control theory prediction [25]. The lineage tracing evidences are from two earlier studies [23], [24]. The transition from cell asymmetry to population asymmetry can take a variety of forms, including I) a fast switch similar to the Bang-Bang control, II) a linear accumulation, III) slow progression depending on the interplay between intrinsic and extrinsic signals. (B) When simulating crypt histories using curve I, II and III in Figure 3A and plotting mean pairwise divergence time between two random cells (a measurement of genealogical length), the average pairwise divergence shows very different trajectories under different transitional history.
Mentions: Previous observations revealed that mouse crypt morphogenesis started with a surge of symmetric divisions establishing the pool of stem cells, followed by a transition to predominantly asymmetric divisions that maintain an equilibrium between stem cell self-renewal and differentiation [25]. Our results support the existence of a second transition from mostly asymmetric stem cell divisions to symmetric divisions during intestinal homeostasis (Figure 3A). It remains to be seen whether this phenomenon also occurs in other systems.

Bottom Line: 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 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Computational Biology and Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.

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.

Show MeSH
Related in: MedlinePlus