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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3131-3137.
Prepublished online as a Blood First Edition Paper on December 29, 2005; DOI 10.1182/blood-2005-08-3412.
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HEMATOPOIESIS
Human thymus contains multipotent progenitors with T/B lymphoid, myeloid, and erythroid lineage potential
Floor Weerkamp,
Miranda R. M. Baert,
Martijn H. Brugman,
Willem A. Dik,
Edwin F. E. de Haas,
Trudi P. Visser,
Christianne J. M. de Groot,
Gerard Wagemaker,
Jacques J. M. van Dongen, and
Frank J. T. Staal
From the Department of Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands; the Department of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands; and the Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
It is a longstanding question which bone marrow–derived cell seeds the thymus and to what level this cell is committed to the T-cell lineage. We sought to elucidate this issue by examining gene expression, lineage potential, and self-renewal capacity of the 2 most immature subsets in the human thymus, namely CD34+CD1a– and CD34+CD1a+ thymocytes. DNA microarrays revealed the presence of several myeloid and erythroid transcripts in CD34+CD1a– thymocytes but not in CD34+CD1a+ thymocytes. Lineage potential of both subpopulations was assessed using in vitro colony assays, bone marrow stroma cultures, and in vivo transplantation into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The CD34+CD1a– subset contained progenitors with lymphoid (both T and B), myeloid, and erythroid lineage potential. Remarkably, development of CD34+CD1a– thymocytes toward the T-cell lineage, as shown by T-cell receptor  gene rearrangements, could be reversed into a myeloid-cell fate. In contrast, the CD34+CD1a+ cells yielded only T-cell progenitors, demonstrating their irreversible commitment to the T-cell lineage. Both CD34+CD1a– and CD34+CD1a+ thymocytes failed to repopulate NOD/SCID mice. We conclude that the human thymus is seeded by multipotent progenitors with a much broader lineage potential than previously assumed. These cells resemble hematopoietic stem cells but, by analogy with murine thymocytes, apparently lack sufficient self-renewal capacity.
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