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

Blood. 2004 Dec 15;104(13):3918-26. doi: 10.1182/blood-2004-05-1845. Epub 2004 Aug 26.


The early stages of human lymphopoiesis are poorly characterized. Here, we compared the lymphoid potential of a novel umbilical cord blood CD34(+)CD45RA(hi)CD7(+) hematopoietic progenitor cell (HPC) population with that of CD34(+)CD45RA(hi)Lin(-)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(+)CD45RA(hi)CD7(+) HPCs could generate cells of the 3 lymphoid lineages, their potential was skewed toward the T/natural killer (T/NK) lineages. In contrast, CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs predominantly exhibited a B-cell potential. Gene expression profiling with DNA microarrays confirmed that CD34(+)CD45RA(hi)CD7(+) HPCs selectively expressed T-lymphoid and NK lineage-committed genes while retaining expression of genes affiliated to the granulomonocytic lineage, whereas CD34(+)CD45RA(hi)Lin(-)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(+)CD45RA(int)CD7(-) and CD34(+)CD45RA(hi)Lin(-) HPCs with mixed lymphomyeloid potential, from which they emerged independently with different growth/differentiation factor requirements. These findings indicate that CD34(+)CD45RA(hi)CD7(+) and CD34(+)CD45RA(hi)Lin(-)CD10(+) HPCs correspond to multipotent early lymphoid progenitors polarized toward either the T/NK or B lineage, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / blood
  • Antigens, CD34 / blood
  • B-Lymphocytes / immunology*
  • Cell Culture Techniques / methods
  • Cell Differentiation
  • Colony-Forming Units Assay
  • Fetal Blood / immunology*
  • Hematopoietic Stem Cells / immunology*
  • Humans
  • Immunophenotyping
  • Infant, Newborn
  • Killer Cells, Natural / immunology*
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, CD34