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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.
IMMUNOBIOLOGY Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7– lympho-myeloid thymic progenitors1 Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA
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% to 2% of progenitors are CD7–. 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, that is, the CD7hi fraction produced T and NK cells but lacked B and myelo-erythroid potential, the CD7int (CD10+) fraction produced B, T, and NK cells, but lacked myelo-erythroid potential. The CD7– fraction produced all lymphoid and myelo-erythroid lineages and expressed HSC-associated genes. However, CD34+lin–CD7– thymocytes also expressed early T lymphoid genes Tdt, pT
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