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TISSUE-SPECIFIC STEM CELLS

The HOXB4 Homeoprotein Differentially Promotes Ex Vivo Expansion of Early Human Lymphoid Progenitors

^aInstitut Cochin, Département d'Hématologie, Paris, France;
^bInstitut National de la Santé et de la Recherche Médicale, U567, Paris, France;
^cCentre National de la Recherche Scientifique, Unité Mixte de Recherche 8104 Paris, France;
^dFaculté de Médecine René Descartes, Université Paris, Unité Mixte 3, Paris, France;
^eFaculté de Médecine Paris-Sud 11, Université Paris-Sud, le Kremlin-Bicêtre, France;
^fInstitut National de la Santé et de la Recherche Médicale, U753, and
^gCentre d'Investigation Clinique Biothérapies, Institut Gustave Roussy, Villejuif, France

Key Words. Human hematopoiesis • Umbilical cord blood • Cell expansion • Lymphoid progenitors • HOXB4

Correspondence: Serge Fichelson, M.D., Ph.D., U567, Département d'Hématologie, Institut Cochin, Maternité Port-Royal, 123 Boulevard de Port-Royal, 75014 Paris, France. Telephone: 33-1-53-10-43-81; Fax: 33-1-43-25-11-67; e-mail: fichelson{at}cochin.inserm.fr

Received September 4, 2007; accepted for publication October 18, 2007.
First published online in STEM CELLS EXPRESS   October 25, 2007.



The HOXB4 homeoprotein is known to promote the expansion of mouse and human hematopoietic stem cells (HSCs) and progenitors of the myeloid lineages. However, the putative involvement of HOXB4 in lymphopoiesis and particularly in the expansion of early lymphoid progenitor cells has remained elusive. Based on the ability of the HOXB4 protein to passively enter hematopoietic cells, our group previously designed a long-term culture procedure of human HSCs that allows ex vivo expansion of these cells. Here, this method has been further used to investigate whether HOXB4 could cause similar expansion on cells originating from CD34⁺ hematopoietic progenitor cells (HPCs) committed at various levels toward the lymphoid lineages. We provide evidence that HOXB4 protein delivery promotes the expansion of primitive HPCs that generate lymphoid progenitors. Moreover, HOXB4 acts on lymphomyeloid HPCs and committed T/natural killer HPCs but not on primary B-cell progenitors. Our results clarify the effect of HOXB4 in the early stages of human lymphopoiesis, emphasizing the contribution of this homeoprotein in the maintenance of the intrinsic lymphomyeloid differentiation potential of defined HPC subsets. Finally, this study supports the potential use of HOXB4 protein for HSC and HPC expansion in a therapeutic setting and furthers our understanding of the mechanisms of the molecular regulation of hematopoiesis.

Disclosure of potential conflicts of interest is found at the end of this article.