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An animated landscape representation of CD4+ T-cell differentiation, variability, and plasticity: insights into the behavior of populations versus cells.

ABSTRACT: Recent advances in understanding CD4(+) T-cell differentiation suggest that previous models of a few distinct, stable effector phenotypes were too simplistic. Although several well-characterized phenotypes are still recognized, some states display plasticity, and intermediate phenotypes exist. As a framework for reexamining these concepts, we use Waddington's landscape paradigm, augmented with explicit consideration of stochastic variations. Our animation program "LAVA" visualizes T-cell differentiation as cells moving across a landscape of hills and valleys, leading to attractor basins representing stable or semistable differentiation states. The model illustrates several principles, including: (i) cell populations may behave more predictably than individual cells; (ii) analogous to reticulate evolution, differentiation may proceed through a network of interconnected states, rather than a single well-defined pathway; (iii) relatively minor changes in the barriers between attractor basins can change the stability or plasticity of a population; (iv) intrapopulation variability of gene expression may be an important regulator of differentiation, rather than inconsequential noise; (v) the behavior of some populations may be defined mainly by the behavior of outlier cells. While not a quantitative representation of actual differentiation, our model is intended to provoke discussion of T-cell differentiation pathways, particularly highlighting a probabilistic view of transitions between states.

SUBMITTER: Rebhahn JA

PROVIDER: S-EPMC4209377 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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An animated landscape representation of CD4+ T-cell differentiation, variability, and plasticity: insights into the behavior of populations versus cells.

Rebhahn Jonathan A JA Deng Nan N Sharma Gaurav G Livingstone Alexandra M AM Huang Sui S Mosmann Tim R TR

European journal of immunology 20140801 8

Recent advances in understanding CD4(+) T-cell differentiation suggest that previous models of a few distinct, stable effector phenotypes were too simplistic. Although several well-characterized phenotypes are still recognized, some states display plasticity, and intermediate phenotypes exist. As a framework for reexamining these concepts, we use Waddington's landscape paradigm, augmented with explicit consideration of stochastic variations. Our animation program "LAVA" visualizes T-cell differe ...[more]

PMID: 24945794

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Dataset Information

An animated landscape representation of CD4+ T-cell differentiation, variability, and plasticity: insights into the behavior of populations versus cells.

Publications

An animated landscape representation of CD4+ T-cell differentiation, variability, and plasticity: insights into the behavior of populations versus cells.

Similar Datasets

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