Virally mediated MafB transduction induces the monocyte commitment of human CD34+ hematopoietic stem/progenitor cells.
Gemelli C,
Montanari M,
Tenedini E,
Zanocco Marani T,
Vignudelli T,
Siena M,
Zini R,
Salati S,
Tagliafico E,
Manfredini R,
Grande A,
Ferrari S.
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Upregulation of specific transcription factors is a generally accepted mechanism to explain the commitment of hematopoietic stem cells along precise maturation lineages. Based on this premise, transduction of primary hematopoietic stem/progenitor cells with viral vectors containing the investigated transcription factors appears as a suitable experimental model to identify such regulators. Although MafB transcription factor is believed to play a role in the regulation of monocytic commitment, no demonstration is, to date, available supporting this function in normal human hematopoiesis. To address this issue, we retrovirally transduced cord blood CD34+ hematopoietic progenitors with a MafB cDNA. Immunophenotypic and morphological analysis of transduced cells demonstrated the induction of a remarkable monomacrophage differentiation. Microarray analysis confirmed these findings and disclosed the upregulation of macrophage-related transcription factors belonging to the AP-1, MAF, PPAR and MiT families. Altogether our data allow to conclude that MafB is a key regulator of human monocytopoiesis.
PMID: 16456583 [PubMed - indexed for MEDLINE]