Asymmetric cell division during T cell development controls downstream fate
Open accessAbstract
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, Scribble, or the altered inheritance of fate determinants impacts subsequent fate decisions to influence the numbers of DN4 cells arising after the β-selection checkpoint. These findings indicate that ACD enables the thymic microenvironment to orchestrate fate decisions related to differentiation and self-renewal.
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Mammalian Scribble has a similar role in the immune system: asymmetric cell division and subsequent asymmetric distribution of fate determinants require Scribble function, shaping the relative numbers of different T cell subsets.
“Mammalian Scribble has a strikingly similar role in the immune system. Asymmetric cell division and subsequent asymmetric distribution of fate determinants (some shared with fly neuroblasts) both require Scribble function, shaping the relative numbers of different T cell subsets (Pham et al., 2015).”
From Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation (2019) · cites this paper as Pham et al., 2015
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References 68 · Cited by 39
- Authors
- Pham, K., Shimoni, R., Charnley, M., Ludford-Menting, M. J., Hawkins, E. D., Ramsbottom, K., Oliaro, J., Izon, D., Ting, S. B., Reynolds, J., Lythe, G., Molina-Paris, C., Melichar, H., Robey, E., Humbert, P. O., Gu, M., & Russell, S. M.
- Affiliations
- Peter MacCallum Cancer Centre (AU)
- Immune Signalling Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia 1
- The University of Melbourne (AU)
- St Vincents Institute of Medical Research (AU)
- University of Leeds (GB)
- Department of Applied Mathematics, School of Mathematics, University of Leeds, Leeds LS2 9JT, England, UK 9
- University of California, Berkeley (US)
- Swinburne University of Technology (AU)
- Corresponding author
- Russell, Sarah M.
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2015-09-14
- Volume
- 210
- Issue
- 6
- Pages
- 933-950
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC4576854
- OpenAlex
- W2117937562
- Cited by
- 39
- References
- 68
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 7 · 2018: 6 · 2017: 3 · 2016: 1 · 2015: 1
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion, cc-by-nc-sa)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-sa)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion, cc-by-nc-sa)
- Swinburne figshare (Swinburne University of Technology)
- Funders
- National Science Foundation
- Australian National Fabrication Facility
- Australian Cancer Research Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (154664)
- Swinburne University of Technology
- University of Toronto
- Peter MacCallum Cancer Centre
- Biotechnology and Biological Sciences Research Council (BB/F003811/1, BB/G023395/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- asymmetric cell division, T cell development, beta-selection, Numb, alpha-adaptin, cell fate determination, cell polarity, Scribble, stromal interactions, chemokine receptor signaling, thymic microenvironment, self-renewal, clonal expansion
- MeSH terms
- Animals, Cell Communication, Cell Differentiation, Cells, Cultured, Membrane Proteins, Mice, Inbred C57BL, Nerve Tissue Proteins, Phosphorylation, Protein Kinase C, Thymus Gland, Time Factors, Transfection, Signal Transduction, Cell Polarity, Cell Death, Stromal Cells, Mice, Knockout, Models, Immunological, Coculture Techniques, Receptors, CXCR4, Adaptor Protein Complex alpha Subunits, Intracellular Signaling Peptides and Proteins, Cell Proliferation, Asymmetric Cell Division, Thymocytes, Cellular Microenvironment
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