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Blood, 15 December 2004, Vol. 104, No. 13, pp. 3918-3926.
Prepublished online as a Blood First Edition Paper on August 26, 2004; DOI 10.1182/blood-2004-05-1845.
Previous Article | Next Article 
Submitted May 14, 2004
Accepted July 28, 2004
Molecular characterization of early human T/NK and B lymphoid progenitor cells in umbilical cord blood
Rima Haddad, Philippe Guardiola, Brigitte Izac, Christelle Thibault, Jerry Radich, Anne-Lise Delezoide, Claude Baillou, Francois M Lemoine, Jean Claude Gluckman, Francoise Pflumio, and Bruno Canque*
EMI-0013 Institut National de la Sante et de la Recherche Medicale, Universite Paris 7, and Laboratoire d'Immunologie Cellulaire et Immunopathologie de l'Ecole Pratique des Hautes Etudes, Institut Universitaire d'Hematologie, hopital Saint-Louis, Paris, France
Experimental Pathology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Departement d'Hematologie, Institut Cochin, INSERM U567, Paris, France
Institut de Genetique et Biologie Moleculaire et Cellulaire, Strasbourg, France
Service de Biologie du Developpement, hopital Robert Debre AP-HP, Paris, France
CNRS UMR 7087, hopital Pitie-Salpetriere AP-HP, Paris, France
* Corresponding author; email: bruno.canque{at}chu-stlouis.fr.
Abstract
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 three lymphoid lineages, their potential was skewed toward the T/NK lineages. In contrast, CD34+CD45RAhiLin-CD10+ HPCs predominantly exhibited a B cell potential. Gene expression profiling with DNA micro-arrays confirmed that CD34+CD45RAhiCD7+ HPCs selectively expressed T-lymphoid and NK lineage-committed genes while retaining expression of genes affiliated to the granulo-monocytic 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 lympho-myeloid 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.

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