title: The HOXB4 homeoprotein differentially promotes ex vivo expansion of early human lymphoid progenitors.
abstract: 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.
authors.affiliation: Institut Cochin, Département d'Hématologie, Paris, France.
authors.forename: Rima
authors.initials: R
authors.lastname: Haddad
authors.forename: Françoise
authors.initials: F
authors.lastname: Pflumio
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vigon
authors.forename: Géraldine
authors.initials: G
authors.lastname: Visentin
authors.forename: Céline
authors.initials: C
authors.lastname: Auvray
authors.forename: Serge
authors.initials: S
authors.lastname: Fichelson
authors.forename: Sophie
authors.initials: S
authors.lastname: Amsellem
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D038041:Lymphopoiesis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010641:Phenotype; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014161:Transduction, Genetic
chemical_list: D015703:Antigens, CD; C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors