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GATA3 induces human T-cell commitment by restraining Notch activity and repressing NK-cell fate

Inge Van de Walle (UGent) , Anne-Catherine Dolens (UGent) , Kaat Durinck (UGent) , Katrien De Mulder (UGent) , Wouter Van Loocke (UGent) , Sagar Damle, Els Waegemans (UGent) , Jelle De Medts (UGent) , Imke Velghe (UGent) , Magda De Smedt (UGent) , et al.
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Abstract
The gradual reprogramming of haematopoietic precursors into the T-cell fate is characterized by at least two sequential developmental stages. Following Notch1-dependent T-cell lineage specification during which the first T-cell lineage genes are expressed and myeloid and dendritic cell potential is lost, T-cell specific transcription factors subsequently induce T-cell commitment by repressing residual natural killer (NK)-cell potential. How these processes are regulated in human is poorly understood, especially since efficient T-cell lineage commitment requires a reduction in Notch signalling activity following T-cell specification. Here, we show that GATA3, in contrast to TCF1, controls human T-cell lineage commitment through direct regulation of three distinct processes: repression of NK-cell fate, upregulation of T-cell lineage genes to promote further differentiation and restraint of Notch activity. Repression of the Notch1 target gene DTX1 hereby is essential to prevent NK-cell differentiation. Thus, GATA3-mediated positive and negative feedback mechanisms control human T-cell lineage commitment.
Keywords
MOUSE, ACUTE LYMPHOBLASTIC-LEUKEMIA, TARGET, CHECKPOINT, EXPRESSION, DIFFERENTIATION, ALPHA-BETA, TRANSCRIPTIONAL CONTROL, LINEAGE SPECIFICATION, RECEPTOR-LIGAND INTERACTIONS

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Chicago
Van de Walle, Inge, Anne-Catherine Dolens, Kaat Durinck, Katrien De Mulder, Wouter Van Loocke, Sagar Damle, Els Waegemans, et al. 2016. “GATA3 Induces Human T-cell Commitment by Restraining Notch Activity and Repressing NK-cell Fate.” Nature Communications 7.
APA
Van de Walle, I., Dolens, A.-C., Durinck, K., De Mulder, K., Van Loocke, W., Damle, S., Waegemans, E., et al. (2016). GATA3 induces human T-cell commitment by restraining Notch activity and repressing NK-cell fate. NATURE COMMUNICATIONS, 7.
Vancouver
1.
Van de Walle I, Dolens A-C, Durinck K, De Mulder K, Van Loocke W, Damle S, et al. GATA3 induces human T-cell commitment by restraining Notch activity and repressing NK-cell fate. NATURE COMMUNICATIONS. 2016;7.
MLA
Van de Walle, Inge, Anne-Catherine Dolens, Kaat Durinck, et al. “GATA3 Induces Human T-cell Commitment by Restraining Notch Activity and Repressing NK-cell Fate.” NATURE COMMUNICATIONS 7 (2016): n. pag. Print.
@article{7249167,
  abstract     = {The gradual reprogramming of haematopoietic precursors into the T-cell fate is characterized by at least two sequential developmental stages. Following Notch1-dependent T-cell lineage specification during which the first T-cell lineage genes are expressed and myeloid and dendritic cell potential is lost, T-cell specific transcription factors subsequently induce T-cell commitment by repressing residual natural killer (NK)-cell potential. How these processes are regulated in human is poorly understood, especially since efficient T-cell lineage commitment requires a reduction in Notch signalling activity following T-cell specification. Here, we show that GATA3, in contrast to TCF1, controls human T-cell lineage commitment through direct regulation of three distinct processes: repression of NK-cell fate, upregulation of T-cell lineage genes to promote further differentiation and restraint of Notch activity. Repression of the Notch1 target gene DTX1 hereby is essential to prevent NK-cell differentiation. Thus, GATA3-mediated positive and negative feedback mechanisms control human T-cell lineage commitment.},
  articleno    = {11171},
  author       = {Van de Walle, Inge and Dolens, Anne-Catherine and Durinck, Kaat and De Mulder, Katrien and Van Loocke, Wouter and Damle, Sagar and Waegemans, Els and De Medts, Jelle and Velghe, Imke and De Smedt, Magda and Vandekerckhove, Bart and Kerre, Tessa and Plum, Jean and Leclercq, Georges and Rothenberg, Ellen V and Van Vlierberghe, Pieter and Speleman, Franki and Taghon, Tom},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keyword      = {MOUSE,ACUTE LYMPHOBLASTIC-LEUKEMIA,TARGET,CHECKPOINT,EXPRESSION,DIFFERENTIATION,ALPHA-BETA,TRANSCRIPTIONAL CONTROL,LINEAGE SPECIFICATION,RECEPTOR-LIGAND INTERACTIONS},
  language     = {eng},
  pages        = {14},
  title        = {GATA3 induces human T-cell commitment by restraining Notch activity and repressing NK-cell fate},
  url          = {http://dx.doi.org/10.1038/ncomms11171},
  volume       = {7},
  year         = {2016},
}

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