Virally mediated MafB transduction induces the monocyte commitment of human CD34+ hematopoietic stem/progenitor cells.
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.
Gemelli
C
C
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Montanari
M
M
Tenedini
E
E
Zanocco Marani
T
T
Vignudelli
T
T
Siena
M
M
Zini
R
R
Salati
S
S
Tagliafico
E
E
Manfredini
R
R
Grande
A
A
Ferrari
S
S
D018952:Antigens, CD34 / Q000378:metabolism; D002460:Cell Line; D003114:Colony-Forming Units Assay; D018076:DNA, Complementary / Q000235:genetics; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D051258:MafB Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D038042:Myelopoiesis; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D015854:Up-Regulation
D018952:Antigens, CD34; D018076:DNA, Complementary; C490407:MAFB protein, human; D051258:MafB Transcription Factor; D034741:RNA, Small Interfering