Ghent University Academic Bibliography

Advanced

Generation of T cells from human embryonic stem cell-derived hematopoietic zones

FRANK TIMMERMANS UGent, Imke Velghe UGent, Lieve Vanwalleghem, Magda De Smedt UGent, Stefanie Van Coppernolle UGent, Tom Taghon UGent, Harry Moore, Georges Leclercq UGent, Anton Langerak and Tessa Kerre UGent, et al. (2009) JOURNAL OF IMMUNOLOGY. 182(11). p.6879-6888
abstract
Human embryonic stem cells (hESC) are pluripotent stem cells. A major challenge in the field of hESC is the establishment of specific differentiation protocols that drives hESC down a particular lineage fate. So far, attempts to generate T cells from hESC in vitro were unsuccessful. In this study, we show that T cells can be generated in vitro from hESC-derived hematopoietic precursor cells present in hematopoietic zones (HZs). These zones are morphologically similar to blood islands during embryonic development, and are formed when hESC are cultured on OP9 stromal cells. Upon subsequent transfer of these HZs on OP9 cells expressing high levels of Delta-like 1 and in the presence of growth factors, cells expand and differentiate to T cells. Furthermore, we show that T cells derive exclusively from a CD3(high)CD43(low) population, further substantiating the notion that hESC-derived CD34(high)CD43(low) cells are formed in HZs and are the only population containing multipotent hematopoietic precursor cells. Differentiation to T cells sequentially passes through the physiological intermediates: CD34(+)CD7(+) T/NK committed, CD7(+)CD4(+)CD8(-) immature single positive, CD4(+)CD8(+) double positive, and finally CD3(+)CD1(-)CD27(+) mature T cell stages. TCR alpha beta(+) and TCR gamma delta(+) T cells are generated. Mature T cells are polyclonal, proliferate, and secrete cytokines in response to mitogens. This protocol for the de novo generation of T cells from hESC could be clinically and scientifically relevant.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
THYMUS, DIFFERENTIATION, IDENTIFICATION, EXPRESSION, INDUCTION, PRECURSORS, DELTA-LIKE-1 IN-VITRO, PROGENITOR CELLS, CORD BLOOD, STROMAL CELLS
journal title
JOURNAL OF IMMUNOLOGY
J. Immunol.
volume
182
issue
11
pages
6879 - 6888
Web of Science type
Article
Web of Science id
000266258300031
JCR category
IMMUNOLOGY
JCR impact factor
5.646 (2009)
JCR rank
18/126 (2009)
JCR quartile
1 (2009)
ISSN
0022-1767
DOI
10.4049/jimmunol.0803670
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
693318
handle
http://hdl.handle.net/1854/LU-693318
date created
2009-06-12 12:25:01
date last changed
2011-04-20 16:17:00
@article{693318,
  abstract     = {Human embryonic stem cells (hESC) are pluripotent stem cells. A major challenge in the field of hESC is the establishment of specific differentiation protocols that drives hESC down a particular lineage fate. So far, attempts to generate T cells from hESC in vitro were unsuccessful. In this study, we show that T cells can be generated in vitro from hESC-derived hematopoietic precursor cells present in hematopoietic zones (HZs). These zones are morphologically similar to blood islands during embryonic development, and are formed when hESC are cultured on OP9 stromal cells. Upon subsequent transfer of these HZs on OP9 cells expressing high levels of Delta-like 1 and in the presence of growth factors, cells expand and differentiate to T cells. Furthermore, we show that T cells derive exclusively from a CD3(high)CD43(low) population, further substantiating the notion that hESC-derived CD34(high)CD43(low) cells are formed in HZs and are the only population containing multipotent hematopoietic precursor cells. Differentiation to T cells sequentially passes through the physiological intermediates: CD34(+)CD7(+) T/NK committed, CD7(+)CD4(+)CD8(-) immature single positive, CD4(+)CD8(+) double positive, and finally CD3(+)CD1(-)CD27(+) mature T cell stages. TCR alpha beta(+) and TCR gamma delta(+) T cells are generated. Mature T cells are polyclonal, proliferate, and secrete cytokines in response to mitogens. This protocol for the de novo generation of T cells from hESC could be clinically and scientifically relevant.},
  author       = {TIMMERMANS, FRANK and Velghe, Imke and Vanwalleghem, Lieve and De Smedt, Magda and Van Coppernolle, Stefanie and Taghon, Tom and Moore, Harry and Leclercq, Georges and Langerak, Anton and Kerre, Tessa and Plum, Jean and Vandekerckhove, Bart},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keyword      = {THYMUS,DIFFERENTIATION,IDENTIFICATION,EXPRESSION,INDUCTION,PRECURSORS,DELTA-LIKE-1 IN-VITRO,PROGENITOR CELLS,CORD BLOOD,STROMAL CELLS},
  language     = {eng},
  number       = {11},
  pages        = {6879--6888},
  title        = {Generation of T cells from human embryonic stem cell-derived hematopoietic zones},
  url          = {http://dx.doi.org/10.4049/jimmunol.0803670},
  volume       = {182},
  year         = {2009},
}

Chicago
TIMMERMANS, FRANK, Imke Velghe, Lieve Vanwalleghem, Magda De Smedt, Stefanie Van Coppernolle, Tom Taghon, Harry Moore, et al. 2009. “Generation of T Cells from Human Embryonic Stem Cell-derived Hematopoietic Zones.” Journal of Immunology 182 (11): 6879–6888.
APA
TIMMERMANS, F., Velghe, I., Vanwalleghem, L., De Smedt, M., Van Coppernolle, S., Taghon, T., Moore, H., et al. (2009). Generation of T cells from human embryonic stem cell-derived hematopoietic zones. JOURNAL OF IMMUNOLOGY, 182(11), 6879–6888.
Vancouver
1.
TIMMERMANS F, Velghe I, Vanwalleghem L, De Smedt M, Van Coppernolle S, Taghon T, et al. Generation of T cells from human embryonic stem cell-derived hematopoietic zones. JOURNAL OF IMMUNOLOGY. 2009;182(11):6879–88.
MLA
TIMMERMANS, FRANK, Imke Velghe, Lieve Vanwalleghem, et al. “Generation of T Cells from Human Embryonic Stem Cell-derived Hematopoietic Zones.” JOURNAL OF IMMUNOLOGY 182.11 (2009): 6879–6888. Print.