Human thymus contains multipotent progenitors with T/B lymphoid, myeloid, and erythroid lineage potential.
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 delta 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.
Weerkamp
Floor
F
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Baert
Miranda R M
MR
Brugman
Martijn H
MH
Dik
Willem A
WA
de Haas
Edwin F E
EF
Visser
Trudi P
TP
de Groot
Christianne J M
CJ
Wagemaker
Gerard
G
van Dongen
Jacques J M
JJ
Staal
Frank J T
FJ
D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D003114:Colony-Forming Units Assay / Q000379:methods; D015329:Gene Rearrangement, T-Lymphocyte / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*
D018949:Antigens, CD1; D018952:Antigens, CD34; C419393:CD1a antigen; D016692:Receptors, Antigen, T-Cell, gamma-delta