Virally mediated MafB transduction induces the monocyte commitment of human CD34+ hematopoietic stem/progenitor cells

Abstract

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 þ 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.

MafB promotes atherosclerosis by inhibiting foam-cell apoptosis

“…In haematopoietic lineages, MafB is expressed selectively in monocytes and macrophages but not in other mature myeloid or lymphoid lineages 18,21,22 . In vitro studies have demonstrated that MafB induces myelomonocytic differentiation in immortalized myeloblasts and human CD34 þ haematopoietic stem cells 18,[23][24][25] . However, Mafb-deficient embryos retain a normal population of Mac-1-positive myeloid cells, although these cells fail to express the F4/80 marker for differentiated resident macrophages 26 .…”

Differential expression of Wnt13 isoforms during leukemic cell differentiation

“…MAF-B interaction with ets transcription factor appears to be required for the down-regulation of erythroid genes such as ß-globin (28) and the up-regulation of the CD41 marker during the megakaryocytic differentiation (27). Moreover, MAF-B is crucial for the differentiation of non-adherent macrophages and expression of the macrophage marker F4/80 (41) as well as for the control of the balance between dendritic and monocytic differentiation (25,26,42). The fact that the factors involved in a specific cellular process display similar gene expression patterns reinforces the possibility that the Wnt13 isoforms constitute additional players in the differentiation process towards monocyte/macrophages.…”

“…2). The expression of the transcription factor MAF-B was followed since its expression was associated with monocyte/macrophage (25,26) and megakaryocytic differentiation (27,28).…”

HSP70 Is Associated with Endothelial Activation in Placental Vascular Diseases

“…This gene is a member of the Maf family of bZIP transcription factors that are involved generally in cellular differentiation (28). MAFB is a putative tumor suppressor in the myeloid lineage, with a key role in monopoiesis (29) as well as monocyte-dendritic cell differentiation (30). Little is known about the biology of this gene in the context of inflammatory disease.…”