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Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment

Magda De Smedt (UGent) , Inge Hoebeke (UGent) , Katia Reynvoet (UGent) , Georges Leclercq (UGent) and Jean Plum (UGent)
(2005) BLOOD. 106(10). p.3498-3506
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Abstract
Notch receptors are involved in lineage decisions in multiple developmental scenarios, including hematopoiesis. Here, we treated hybrid human-mouse fetal thymus organ culture with the gamma-secretase inhibitor 7 (N-[N-(3,5-difluorophenyl)-Lalanyl]-S-phenyl-glycine t-butyl ester) (DAPT) to establish the role of Notch signaling in human hematopoietic lineage decisions. The effect of inhibition of Notch signaling was studied starting from cord blood CD34(+) or thymic CD34(+)CD1(-), CD34(+)CD1(+), or CD4ISP progenitors. Treatment of cord blood CD34(+) cells with low DAPT concentrations results in aberrant CD4ISP and CD4/CD8 double-positive (DP) thymocytes, which are negative for intracellular T-cell receptor beta (TCR beta). On culture with intermediate and high DAPT concentrations, thymic CD34(+)CD1(-) cells still generate aberrant intracellular TCR beta(-) DIP cells that have undergone DJ but not VDJ recombination. Inhibition of Notch signaling shifts differentiation into non-T cells in a thymic microenvironment, depending on the starting progenitor cells: thymic CD34(+)CD1(+) cells do not generate non-T cells, thymic CD34(+)CD1(-) cells generate INK cells and monocytic/dendritic cells, and cord blood CD34(+)Lin(-) cells generate B, INK, and monocytic/dendritic cells in the presence of DAPT Our data indicate that Notch signaling is crucial to direct human progenitor cells into the T-cell lineage, whereas it has a negative impact on B, NK, and monocytic/dendritic cell generation in a dose-dependent fashion.
Keywords
HUMAN CORD-BLOOD, HEMATOPOIETIC STEM-CELLS, THYMOCYTE DEVELOPMENT, PROGENITOR CELLS, GENE-EXPRESSION, ALPHA-BETA, ORGAN-CULTURE, FATE, RECEPTOR, INACTIVATION

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MLA
De Smedt, Magda, et al. “Different Thresholds of Notch Signaling Bias Human Precursor Cells toward B-, NK-, Monocytic/Dendritic-, or T-Cell Lineage in Thymus Microenvironment.” BLOOD, vol. 106, no. 10, 2005, pp. 3498–506, doi:10.1182/blood-2005-02-0496.
APA
De Smedt, M., Hoebeke, I., Reynvoet, K., Leclercq, G., & Plum, J. (2005). Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment. BLOOD, 106(10), 3498–3506. https://doi.org/10.1182/blood-2005-02-0496
Chicago author-date
De Smedt, Magda, Inge Hoebeke, Katia Reynvoet, Georges Leclercq, and Jean Plum. 2005. “Different Thresholds of Notch Signaling Bias Human Precursor Cells toward B-, NK-, Monocytic/Dendritic-, or T-Cell Lineage in Thymus Microenvironment.” BLOOD 106 (10): 3498–3506. https://doi.org/10.1182/blood-2005-02-0496.
Chicago author-date (all authors)
De Smedt, Magda, Inge Hoebeke, Katia Reynvoet, Georges Leclercq, and Jean Plum. 2005. “Different Thresholds of Notch Signaling Bias Human Precursor Cells toward B-, NK-, Monocytic/Dendritic-, or T-Cell Lineage in Thymus Microenvironment.” BLOOD 106 (10): 3498–3506. doi:10.1182/blood-2005-02-0496.
Vancouver
1.
De Smedt M, Hoebeke I, Reynvoet K, Leclercq G, Plum J. Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment. BLOOD. 2005;106(10):3498–506.
IEEE
[1]
M. De Smedt, I. Hoebeke, K. Reynvoet, G. Leclercq, and J. Plum, “Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment,” BLOOD, vol. 106, no. 10, pp. 3498–3506, 2005.
@article{324594,
  abstract     = {{Notch receptors are involved in lineage decisions in multiple developmental scenarios, including hematopoiesis. Here, we treated hybrid human-mouse fetal thymus organ culture with the gamma-secretase inhibitor 7 (N-[N-(3,5-difluorophenyl)-Lalanyl]-S-phenyl-glycine t-butyl ester) (DAPT) to establish the role of Notch signaling in human hematopoietic lineage decisions. The effect of inhibition of Notch signaling was studied starting from cord blood CD34(+) or thymic CD34(+)CD1(-), CD34(+)CD1(+), or CD4ISP progenitors. Treatment of cord blood CD34(+) cells with low DAPT concentrations results in aberrant CD4ISP and CD4/CD8 double-positive (DP) thymocytes, which are negative for intracellular T-cell receptor beta (TCR beta). On culture with intermediate and high DAPT concentrations, thymic CD34(+)CD1(-) cells still generate aberrant intracellular TCR beta(-) DIP cells that have undergone DJ but not VDJ recombination. Inhibition of Notch signaling shifts differentiation into non-T cells in a thymic microenvironment, depending on the starting progenitor cells: thymic CD34(+)CD1(+) cells do not generate non-T cells, thymic CD34(+)CD1(-) cells generate INK cells and monocytic/dendritic cells, and cord blood CD34(+)Lin(-) cells generate B, INK, and monocytic/dendritic cells in the presence of DAPT Our data indicate that Notch signaling is crucial to direct human progenitor cells into the T-cell lineage, whereas it has a negative impact on B, NK, and monocytic/dendritic cell generation in a dose-dependent fashion.}},
  author       = {{De Smedt, Magda and Hoebeke, Inge and Reynvoet, Katia and Leclercq, Georges and Plum, Jean}},
  issn         = {{0006-4971}},
  journal      = {{BLOOD}},
  keywords     = {{HUMAN CORD-BLOOD,HEMATOPOIETIC STEM-CELLS,THYMOCYTE DEVELOPMENT,PROGENITOR CELLS,GENE-EXPRESSION,ALPHA-BETA,ORGAN-CULTURE,FATE,RECEPTOR,INACTIVATION}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{3498--3506}},
  title        = {{Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment}},
  url          = {{http://dx.doi.org/10.1182/blood-2005-02-0496}},
  volume       = {{106}},
  year         = {{2005}},
}

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