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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.


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HEMATOPOIESIS

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, François M. Lemoine, Jean Claude Gluckman, Françoise Pflumio, and Bruno Canque

From the EMI-0013 Institut National de la Santé et de la Recherche Médicale-Université Paris 7, and Laboratoire d'Immunologie Cellulaire et Immunopathologie de l'Ecole Pratique des Hautes Etudes, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France; Experimental Pathology, Fred Hutchinson Cancer Research Center, Seattle WA; Département d'Hématologie, Institut Cochin, Institut National de la Santé et de la Recherche Médicale (INSERM) U567, Paris; Institut de Génétique et Biologie Moléculaire et Cellulaire, Strasbourg, France; Service de Biologie du Développement, Hôpital Robert Debré AP-HP, Paris, France; and the Centre National de la Recherche Scientifique (CNRS) Unite Mixte de Recherche (UMR) 7087, Hôpital Pitié-Salpêtrière AP-HP, Paris, France.

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)


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