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Cellular Senescence: Ex Vivo p53-Dependent Asymmetric Cell Kinetics.

Rambhatla L, Bohn SA, Stadler PB, Boyd JT, Coss RA, Sherley JL - J. Biomed. Biotechnol. (2001)

Bottom Line: Although senescence is a defining property of euploid mammalian cells, its physiologic basis remains obscure.Previously, cell kinetics properties of normal tissue cells have not been considered in models for senescence.In vivo, asymmetric cell kinetics are essential for maintenance of somatic stem cells; ex vivo, the same cell kinetics yield senescence as a simple kinetic endpoint.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Although senescence is a defining property of euploid mammalian cells, its physiologic basis remains obscure. Previously, cell kinetics properties of normal tissue cells have not been considered in models for senescence. We now provide evidence that senescence is in fact the natural consequence of normal in vivo somatic stem cell kinetics extended in culture. This concept of senescence is based on our discovery that cells engineered to conditionally express the well-recognized tumor suppressor protein and senescence factor, p53, exhibit asymmetric cell kinetics. In vivo, asymmetric cell kinetics are essential for maintenance of somatic stem cells; ex vivo, the same cell kinetics yield senescence as a simple kinetic endpoint. This new "asymmetric cell kinetics model" for senescence suggests novel strategies for the isolation and propagation of somatic tissue stem cells in culture.

No MeSH data available.


Related in: MedlinePlus

Division lineages for p53-expressing fibroblasts. Shown are examples of characteristic asymmetric cell kinetics lineages observed in time-lapse analyses of p53-inducible cells (line Ind-8; 26) grownunder inducing conditions (A–D) and presenescent human andmurine embryonic fibroblast cell strains grown under routineculture conditions. (E) and (F), WI-38 cells at passage 18 and26, respectively; (G), wtMEFs at passage 6. Lineages are unevenat end because cell bodies do not indicate passage of time.“Fate uncertain” indicates that a cell either migrated from thefield of view or was not observed for sufficient time to assignits division state with confidence.
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Figure 3: Division lineages for p53-expressing fibroblasts. Shown are examples of characteristic asymmetric cell kinetics lineages observed in time-lapse analyses of p53-inducible cells (line Ind-8; 26) grownunder inducing conditions (A–D) and presenescent human andmurine embryonic fibroblast cell strains grown under routineculture conditions. (E) and (F), WI-38 cells at passage 18 and26, respectively; (G), wtMEFs at passage 6. Lineages are unevenat end because cell bodies do not indicate passage of time.“Fate uncertain” indicates that a cell either migrated from thefield of view or was not observed for sufficient time to assignits division state with confidence.

Mentions: Time-lapse cinematography and digital imaging microscopy wereused to evaluate p53-dependent cell kinetics in several differenttypes of fibroblasts. Division lineages were determined for thep53-inducible murine embryonic fibroblasts; presenescent murineembryonic fibroblasts from wild-type mice (wtMEFs) or mice with ahomozygous disruption of the p53 gene (p53koMEFs; 27); andpresenescent WI-38 human diploid fibroblasts. Examples ofdivision lineages for cells expressing wild-type p53 arediagrammed in Figure 3.


Cellular Senescence: Ex Vivo p53-Dependent Asymmetric Cell Kinetics.

Rambhatla L, Bohn SA, Stadler PB, Boyd JT, Coss RA, Sherley JL - J. Biomed. Biotechnol. (2001)

Division lineages for p53-expressing fibroblasts. Shown are examples of characteristic asymmetric cell kinetics lineages observed in time-lapse analyses of p53-inducible cells (line Ind-8; 26) grownunder inducing conditions (A–D) and presenescent human andmurine embryonic fibroblast cell strains grown under routineculture conditions. (E) and (F), WI-38 cells at passage 18 and26, respectively; (G), wtMEFs at passage 6. Lineages are unevenat end because cell bodies do not indicate passage of time.“Fate uncertain” indicates that a cell either migrated from thefield of view or was not observed for sufficient time to assignits division state with confidence.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC79675&req=5

Figure 3: Division lineages for p53-expressing fibroblasts. Shown are examples of characteristic asymmetric cell kinetics lineages observed in time-lapse analyses of p53-inducible cells (line Ind-8; 26) grownunder inducing conditions (A–D) and presenescent human andmurine embryonic fibroblast cell strains grown under routineculture conditions. (E) and (F), WI-38 cells at passage 18 and26, respectively; (G), wtMEFs at passage 6. Lineages are unevenat end because cell bodies do not indicate passage of time.“Fate uncertain” indicates that a cell either migrated from thefield of view or was not observed for sufficient time to assignits division state with confidence.
Mentions: Time-lapse cinematography and digital imaging microscopy wereused to evaluate p53-dependent cell kinetics in several differenttypes of fibroblasts. Division lineages were determined for thep53-inducible murine embryonic fibroblasts; presenescent murineembryonic fibroblasts from wild-type mice (wtMEFs) or mice with ahomozygous disruption of the p53 gene (p53koMEFs; 27); andpresenescent WI-38 human diploid fibroblasts. Examples ofdivision lineages for cells expressing wild-type p53 arediagrammed in Figure 3.

Bottom Line: Although senescence is a defining property of euploid mammalian cells, its physiologic basis remains obscure.Previously, cell kinetics properties of normal tissue cells have not been considered in models for senescence.In vivo, asymmetric cell kinetics are essential for maintenance of somatic stem cells; ex vivo, the same cell kinetics yield senescence as a simple kinetic endpoint.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Although senescence is a defining property of euploid mammalian cells, its physiologic basis remains obscure. Previously, cell kinetics properties of normal tissue cells have not been considered in models for senescence. We now provide evidence that senescence is in fact the natural consequence of normal in vivo somatic stem cell kinetics extended in culture. This concept of senescence is based on our discovery that cells engineered to conditionally express the well-recognized tumor suppressor protein and senescence factor, p53, exhibit asymmetric cell kinetics. In vivo, asymmetric cell kinetics are essential for maintenance of somatic stem cells; ex vivo, the same cell kinetics yield senescence as a simple kinetic endpoint. This new "asymmetric cell kinetics model" for senescence suggests novel strategies for the isolation and propagation of somatic tissue stem cells in culture.

No MeSH data available.


Related in: MedlinePlus