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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
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Asymmetric cell division during T cell development controls downstream fate.
Kim Pham1, Raz Shimoni1, Mirren Charnley2
1Immune Signalling Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia Centre for Micro-Photonics, Faculty of Science, Engineering, and Technology, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia.
The Journal of Cell Biology
|September 16, 2015
Summary
Asymmetric cell division (ACD) in developing T cells controls cell fate by differentially distributing Numb and α-Adaptin during β-selection. This process, regulated by stromal cells and signaling, impacts T cell differentiation and self-renewal.
Area of Science:
- Immunology
- Developmental Biology
- Cell Biology
Background:
- T cell development requires expansion of specific clones, hinting at asymmetric cell division (ACD).
- Cell fate determination during T cell development is crucial for immune system function.
Purpose of the Study:
- To investigate the role of asymmetric cell division (ACD) in mammalian T cell development.
- To elucidate the mechanisms and consequences of ACD in T cell fate decisions.
Main Methods:
- Studied T cell development in mammals, focusing on the β-selection stage.
- Analyzed the inheritance of cell fate determinants Numb and α-Adaptin during cell division.
- Investigated the role of stromal cell interactions and chemokine receptor signaling in ACD.
- Examined the impact of polarity regulator (Scribble) deletion on T cell development.
Main Results:
- Asymmetric cell division (ACD) occurs during the β-selection stage of T cell development, with subsequent divisions being symmetric.
- Differential inheritance of Numb and α-Adaptin via ACD controls T cell fate.
- ACD is regulated by stromal cell interactions, chemokine receptor signaling, and polarity regulators.
- Disrupting polarity or altering fate determinant inheritance affects the number of DN4 cells post-β-selection.
Conclusions:
- Asymmetric cell division (ACD) is a key mechanism controlling T cell fate during development.
- The thymic microenvironment utilizes ACD to orchestrate T cell differentiation and self-renewal.
- Differential inheritance of Numb and α-Adaptin by ACD is critical for T cell development outcomes.
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