|
|
Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2003-01-0224.

Submitted January 24, 2003
Accepted April 26, 2003
In vitro generation of T lymphocytes from embryonic stem cell-derived pre-hematopoietic progenitors
Renee F de Pooter, Sarah K Cho, James R Carlyle, and Juan Carlos Zuniga-Pflucker*
Department of Immunology, University of Toronto, Toronto, Ontario, Canada
* Corresponding author; email: jc.zuniga.pflucker{at}utoronto.ca.
Embryonic stem (ES) cells can differentiate into most blood cells in vitro, providing a powerful model system to study hematopoiesis. However, ES cell-derived T lymphocytes have not been generated in vitro, and it was unresolved whether such potential is absent or merely difficult to isolate. As the latter case might result from rapid commitment to non-T cell fates, we isolated ES cell-derived pre-hematopoietic precursors for reconstitution of fetal thymic organ cultures. We found a transient Flk1+ CD45- subset of these precursors generated T lymphocytes in vitro, and the use of reaggregate thymic organ cultures greatly enhanced reconstitution frequency. These findings reveal that ES cells can exhibit in vitro T cell potential, but this is restricted to early stages of ES cell differentiation. Moreover, the results support the notion that the thymic microenvironment can induce T cell differentiation from a subset of pre-hematopoietic progenitors, and suggest deficient migration into intact thymi hindered previous attempts to generate T cells in vitro from ES-cell derived progenitors. These findings demonstrate that a defined subset of ES cells has the potential to generate T cells in vitro, and could contribute to greater understanding of the molecular events of hematopoietic induction and T cell lineage commitment.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
D. S. Kaufman
Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells
Blood,
October 22, 2009;
114(17):
3513 - 3523.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. F. Hutton, T. Gargett, T. J. Sadlon, S. Bresatz, C. Y. Brown, H. Zola, M. F. Shannon, R. J. D'Andrea, and S. C. Barry
Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells
J. Leukoc. Biol.,
March 1, 2009;
85(3):
445 - 451.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. J. Lugus, C. Park, Y. D. Ma, and K. Choi
Both primitive and definitive blood cells are derived from Flk-1+ mesoderm
Blood,
January 15, 2009;
113(3):
563 - 566.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Galic, S. G. Kitchen, A. Kacena, A. Subramanian, B. Burke, R. Cortado, and J. A. Zack
From the Cover: T lineage differentiation from human embryonic stem cells
PNAS,
August 1, 2006;
103(31):
11742 - 11747.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. F. de Pooter, T. M. Schmitt, J. L. de la Pompa, Y. Fujiwara, S. H. Orkin, and J. C. Zuniga-Pflucker
Notch Signaling Requires GATA-2 to Inhibit Myelopoiesis from Embryonic Stem Cells and Primary Hemopoietic Progenitors
J. Immunol.,
May 1, 2006;
176(9):
5267 - 5275.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. L. Olsen, D. L. Stachura, and M. J. Weiss
Designer blood: creating hematopoietic lineages from embryonic stem cells
Blood,
February 15, 2006;
107(4):
1265 - 1275.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Mohtashami and J. C. Zuniga-Pflucker
Cutting Edge: Three-Dimensional Architecture of the Thymus Is Required to Maintain Delta-Like Expression Necessary for Inducing T Cell Development
J. Immunol.,
January 15, 2006;
176(2):
730 - 734.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Huang, K. P. Garrett, R. Pelayo, J. C. Zuniga-Pflucker, H. T. Petrie, and P. W. Kincade
Propensity of Adult Lymphoid Progenitors to Progress to DN2/3 Stage Thymocytes with Notch Receptor Ligation
J. Immunol.,
October 15, 2005;
175(8):
4858 - 4865.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Balciunaite, R. Ceredig, and A. G. Rolink
The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer cell but no B-lymphocyte potential
Blood,
March 1, 2005;
105(5):
1930 - 1936.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Carotta, S. Pilat, A. Mairhofer, U. Schmidt, H. Dolznig, P. Steinlein, and H. Beug
Directed differentiation and mass cultivation of pure erythroid progenitors from mouse embryonic stem cells
Blood,
September 15, 2004;
104(6):
1873 - 1880.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. K. Burt, L. Verda, D.-A. Kim, Y. Oyama, K. Luo, and C. Link
Embryonic Stem Cells As an Alternate Marrow Donor Source: Engraftment without Graft-Versus-Host Disease
J. Exp. Med.,
April 5, 2004;
199(7):
895 - 904.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|