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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1318-1326.
Prepublished online as a Blood First Edition Paper on October 24, 2007; DOI 10.1182/blood-2007-08-106294.
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Submitted August 15, 2007
Accepted October 7, 2007
Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7neg lympho-myeloid thymic progenitors
Qian-Lin Hao, Aswathi A George, Judy Zhu, Lora Barsky, Ewa Zielinska, Xiuli Wang, Mary Price, Shundi Ge, and Gay M. Crooks*
Division of Research Immunology/BMT, Childrens Hospital Los Angeles, Los Angeles, CA, United States
* Corresponding author; email: gcrooks{at}chla.usc.edu.
The identity and lineage potential of the cells that initiate thymopoiesis remain controversial. The goal of these studies was to determine, at a clonal level, the immunophenotype and differentiation pathways of the earliest progenitors in human thymus. Although the majority of human CD34+lin- thymocytes express high levels of CD7, closer analysis reveals that a continuum of CD7 expression exists, and 1-2% of progenitors are CD7neg. CD34+lin- thymocytes were fractionated by CD7 expression and tested for lineage potential in B-lymphoid, T-lymphoid and myeloid-erythroid conditions. Progressive restriction in lineage potential correlated with CD7 expression, i.e. the CD7hi fraction produced T and NK cells but lacked B and myelo-erythroid potential, the CD7dim (CD10+) fraction produced B, T and NK cells, but lacked myelo-erythroid potential. The CD7neg fraction produced all lymphoid and myelo-erythroid lineages and expressed HSC associated genes. However, CD34+lin-CD7neg thymocytes also expressed early T lymphoid genes Tdt, pT and IL-7R and lacked engraftment capacity, suggesting the signals that direct lymphoid commitment and corresponding loss of HSC function are rapidly initiated upon arrival of HSC in the human thymus. Thus, differential levels of CD7 identify the progressive stages of lineage commitment in human thymus, initiated from a primitive CD7neg lympho-myeloid thymic progenitor.
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