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Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development

Anne-Catherine Dolens (UGent) , Kaat Durinck (UGent) , Marieke Lavaert (UGent) , Joni Van der Meulen (UGent) , Imke Velghe (UGent) , Jelle De Medts (UGent) , Karin Weening (UGent) , Juliette Roels (UGent) , Katrien De Mulder (UGent) , Pieter-Jan Volders (UGent) , et al.
(2020) EMBO REPORTS. 21(5).
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Abstract
gamma delta and alpha beta T cells have unique roles in immunity and both originate in the thymus from T-lineage committed precursors through distinct but unclear mechanisms. Here, we show that Notch1 activation is more stringently required for human gamma delta development compared to alpha beta-lineage differentiation and performed paired mRNA and miRNA profiling across 11 discrete developmental stages of human T cell development in an effort to identify the potential Notch1 downstream mechanism. Our data suggest that the miR-17-92 cluster is a Notch1 target in immature thymocytes and that miR-17 can restrict BCL11B expression in these Notch-dependent T cell precursors. We show that enforced miR-17 expression promotes human gamma delta T cell development and, consistently, that BCL11B is absolutely required for alpha beta but less for gamma delta T cell development. This study suggests that human gamma delta T cell development is mediated by a stage-specific Notch-driven negative feedback loop through which miR-17 temporally restricts BCL11B expression and provides functional insights into the developmental role of the disease-associated genes BCL11B and the miR-17-92 cluster in a human context.
Keywords
Genetics, Biochemistry, Molecular Biology

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MLA
Dolens, Anne-Catherine, et al. “Distinct Notch1 and BCL11B Requirements Mediate Human Γδ/Αβ T Cell Development.” EMBO REPORTS, vol. 21, no. 5, 2020, doi:10.15252/embr.201949006.
APA
Dolens, A.-C., Durinck, K., Lavaert, M., Van der Meulen, J., Velghe, I., De Medts, J., … Taghon, T. (2020). Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development. EMBO REPORTS, 21(5). https://doi.org/10.15252/embr.201949006
Chicago author-date
Dolens, Anne-Catherine, Kaat Durinck, Marieke Lavaert, Joni Van der Meulen, Imke Velghe, Jelle De Medts, Karin Weening, et al. 2020. “Distinct Notch1 and BCL11B Requirements Mediate Human Γδ/Αβ T Cell Development.” EMBO REPORTS 21 (5). https://doi.org/10.15252/embr.201949006.
Chicago author-date (all authors)
Dolens, Anne-Catherine, Kaat Durinck, Marieke Lavaert, Joni Van der Meulen, Imke Velghe, Jelle De Medts, Karin Weening, Juliette Roels, Katrien De Mulder, Pieter-Jan Volders, Katleen De Preter, Tessa Kerre, Bart Vandekerckhove, Georges Leclercq, Jo Vandesompele, Pieter Mestdagh, Pieter Van Vlierberghe, Franki Speleman, and Tom Taghon. 2020. “Distinct Notch1 and BCL11B Requirements Mediate Human Γδ/Αβ T Cell Development.” EMBO REPORTS 21 (5). doi:10.15252/embr.201949006.
Vancouver
1.
Dolens A-C, Durinck K, Lavaert M, Van der Meulen J, Velghe I, De Medts J, et al. Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development. EMBO REPORTS. 2020;21(5).
IEEE
[1]
A.-C. Dolens et al., “Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development,” EMBO REPORTS, vol. 21, no. 5, 2020.
@article{8663521,
  abstract     = {{gamma delta and alpha beta T cells have unique roles in immunity and both originate in the thymus from T-lineage committed precursors through distinct but unclear mechanisms. Here, we show that Notch1 activation is more stringently required for human gamma delta development compared to alpha beta-lineage differentiation and performed paired mRNA and miRNA profiling across 11 discrete developmental stages of human T cell development in an effort to identify the potential Notch1 downstream mechanism. Our data suggest that the miR-17-92 cluster is a Notch1 target in immature thymocytes and that miR-17 can restrict BCL11B expression in these Notch-dependent T cell precursors. We show that enforced miR-17 expression promotes human gamma delta T cell development and, consistently, that BCL11B is absolutely required for alpha beta but less for gamma delta T cell development. This study suggests that human gamma delta T cell development is mediated by a stage-specific Notch-driven negative feedback loop through which miR-17 temporally restricts BCL11B expression and provides functional insights into the developmental role of the disease-associated genes BCL11B and the miR-17-92 cluster in a human context.}},
  articleno    = {{e49006}},
  author       = {{Dolens, Anne-Catherine and Durinck, Kaat and Lavaert, Marieke and Van der Meulen, Joni and Velghe, Imke and De Medts, Jelle and Weening, Karin and Roels, Juliette and De Mulder, Katrien and Volders, Pieter-Jan and De Preter, Katleen and Kerre, Tessa and Vandekerckhove, Bart and Leclercq, Georges and Vandesompele, Jo and Mestdagh, Pieter and Van Vlierberghe, Pieter and Speleman, Franki and Taghon, Tom}},
  issn         = {{1469-221X}},
  journal      = {{EMBO REPORTS}},
  keywords     = {{Genetics,Biochemistry,Molecular Biology}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{20}},
  title        = {{Distinct Notch1 and BCL11B requirements mediate human γδ/αβ T cell development}},
  url          = {{http://dx.doi.org/10.15252/embr.201949006}},
  volume       = {{21}},
  year         = {{2020}},
}

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