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(+)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.
Haddad
Rima
R
EMI-0013 Institut National de la Santé et de la Recherche Médicale-Université Paris 7, Laboratoire d'Immunologie Cellulaire et Immunopathologie de l'EcolePratique des Hauntes Etudes, Hôpital Saint-Louis, 75475 Paris CEDEX 10, France.
Guardiola
Philippe
P
Izac
Brigitte
B
Thibault
Christelle
C
Radich
Jerry
J
Delezoide
Anne-Lise
AL
Baillou
Claude
C
Lemoine
François M
FM
Gluckman
Jean Claude
JC
Pflumio
Françoise
F
Canque
Bruno
B
D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D003114:Colony-Forming Units Assay; D005312:Fetal Blood / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D018952:Antigens, CD34