Human thymus contains multipotent progenitors with T/B lymphoid, myeloid, and erythroid lineage potential

• Published in: Blood Vol. 107; no. 8; pp. 3131 - 3137
• Main Authors: Weerkamp, Floor, Baert, Miranda R.M., Brugman, Martijn H., Dik, Willem A., de Haas, Edwin F.E., Visser, Trudi P., de Groot, Christianne J.M., Wagemaker, Gerard, van Dongen, Jacques J.M., Staal, Frank J.T.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-04-2006; The Americain Society of Hematology
• Subjects: Animals; Antigens, CD1 - metabolism; Antigens, CD34 - metabolism; B-Lymphocytes - cytology; B-Lymphocytes - physiology; Biological and medical sciences; Cell Lineage - physiology; Colony-Forming Units Assay - methods; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Rearrangement, T-Lymphocyte - physiology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Humans; Immunobiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Inbred NOD; Mice, SCID; Multipotent Stem Cells - cytology; Multipotent Stem Cells - physiology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - physiology; Thymus Gland - cytology; Thymus Gland - physiology; Human; Lymphoid cell; Lymphopoiesis; Thymus gland; Immunophenotype; Thymocyte; Stem cell; Rodentia; Hematopoietic cell; Cell differentiation; Thymopoiesis; Blood cell; Vertebrata; Mammalia; Mouse; Animal; Multipotent stem cell
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-08-3412

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 δ 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.