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Lineage plasticity and commitment in T-cell development.

Ellen V Rothenberg1, Christopher J Dionne

  • 1Division of Biology, 156-29, California Institute of Technology, Pasadena, CA 91125, USA. evroth@its.caltech.edu

Immunological Reviews
|October 9, 2002
PubMed
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Early T-cell development involves losing potential for other cell types. Conflicting evidence is resolved by overlapping developmental windows and regulatory mechanisms, highlighting transcription factor networks in restricting plasticity.

Area of Science:

  • Immunology
  • Developmental Biology
  • Cell Biology

Background:

  • Intrathymic T-cell development involves losing potential for B, NK, and dendritic cell lineages.
  • Conflicting interpretations exist regarding the order and mechanisms of this lineage potential loss.

Purpose of the Study:

  • To resolve conflicting interpretations of early T-cell development.
  • To investigate the role of regulatory context and transcription factors in developmental plasticity.

Main Methods:

  • Analysis of genetic and cell-transfer studies.
  • Examination of gene expression patterns (SCL, PU.1, Id2) in early thymocytes.
  • In vitro studies involving overexpression of regulatory factors and stimulation of growth factor receptors.
  • Utilizing a cell-line system approximating DN3-stage thymocytes.

Related Experiment Videos

Main Results:

  • A model of overlapping developmental windows and individual pathway regulators reconciles conflicting data.
  • Expression patterns of SCL, PU.1, and Id2 support this model.
  • Overexpression of PU.1 can alter cell specification, even in homogeneous populations, but with discontinuous responses.
  • Developmental plasticity is restricted by specific commitment functions and regulatory context.

Conclusions:

  • Developmental plasticity in early T-cell commitment is regulated by overlapping windows of opportunity.
  • Interacting transcription factor networks play a critical role in restricting lineage plasticity.
  • PU.1 and other regulators influence cell fate decisions within specific developmental stages.