Molecular characterization of early human T/NK and B-lymphoid progenitor cells in umbilical cord blood

The early stages of human lymphopoiesis are poorly characterized. Here, we compared the lymphoid potential of a novel umbilical cord blood CD34+CD45RAhiCD7+ hematopoietic progenitor cell (HPC) population with that of CD34+CD45RAhiLin-CD10+ HPCs, previously proposed as candidate common lymphoid progenitors. Limiting-dilution and clonal analysis, fetal thymic organ cultures, and culture onto Notch ligand Delta-like-1-expressing OP9 cells, showed that although CD34+CD45RAhiCD7+ HPCs could generate cells of the 3 lymphoid lineages, their potential was skewed toward the T/natural killer (T/NK) lineages. In contrast, CD34+CD45RAhiLin-CD10+ HPCs predominantly exhibited a B-cell potential. Gene expression profiling with DNA microarrays confirmed that CD34+CD45RAhiCD7+ HPCs selectively expressed T-lymphoid and NK lineage-committed genes while retaining expression of genes affiliated to the granulomonocytic lineage, whereas CD34+CD45RAhiLin-CD10+ HPCs displayed a typical pro-B-cell transcription profile and essentially lacked genes unrelated to the B lineage. In addition, both populations could be generated in vitro from CD34+CD45RAintCD7- and CD34+CD45RAhiLin- HPCs with mixed lymphomyeloid potential, from which they emerged independently with different growth/differentiation factor requirements. These findings indicate that CD34+CD45RAhiCD7+ and CD34+CD45RAhiLin-CD10+ HPCs correspond to multipotent early lymphoid progenitors polarized toward either the T/NK or B lineage, respectively. (Blood. 2004;104: 3918-3926)