Journal article

Asymmetric cell division during T cell development controls downstream fate

Pham Kim, Raz Shimoni, Mirren Charnley, Mandy J Ludford-Menting, Edwin D Hawkins, Kelly Ramsbottom, Jane Oliaro, David Izon, Stephen B Ting, Joseph Reynolds, Grant Lythe, Carmen Molina-Paris, Heather Melichar, Ellen Robey, Patrick O Humbert, Min Gu, Sarah M Russell



During mammalian T cell development, the requirement for expansion of many individual T cell clones, rather than merely expansion of the entire T cell population, suggests a possible role for asymmetric cell division (ACD). We show that ACD of developing T cells controls cell fate through differential inheritance of cell fate determinants Numb and α-Adaptin. ACD occurs specifically during the β-selection stage of T cell development, and subsequent divisions are predominantly symmetric. ACD is controlled by interaction with stromal cells and chemokine receptor signaling and uses a conserved network of polarity regulators. The disruption of polarity by deletion of the polarity regulator, Scrib..

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Awarded by Human Frontier Science Program

Awarded by Swiss National Science Foundation

Awarded by Biotechnology and Biological Sciences Research Council

Funding Acknowledgements

This work was funded by the Australian National Health and Medical Research Council (project grants and fellowships to E.D. Hawkins, J. Oliaro, S.B. Ting, P.O. Humbert, and S.M. Russell), the Human Frontier Science Program (grant RGP0049), the Australian Research Council (fellowship to S.M. Russell), the Australian Cancer Research Foundation (Cell Biology Program), and the Swiss National Science Foundation (grant P300P3_154664/1 provided funds to M. Charnley). This work benefited from data assembled by the Immgen Consortium (Heng et al., 2008).