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.
Cell Death Differ. 2006 Oct;13(10):1686-96. doi: 10.1038/sj.cdd.4401860. Epub 2006 Feb 3.
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.
特定转录因子的上调是一种被广泛接受的机制，用于解释造血干细胞沿着精确成熟谱系的定向分化。基于这一前提，用携带所研究转录因子的病毒载体转导原代造血干/祖细胞，似乎是鉴定此类调节因子的合适实验模型。尽管MafB转录因子被认为在单核细胞定向分化的调节中起作用，但迄今为止，尚无证据支持其在正常人类造血过程中的这一功能。为了解决这个问题，我们用MafB cDNA逆转录病毒转导脐血CD34+造血祖细胞。对转导细胞的免疫表型和形态分析表明，诱导了显著的单核巨噬细胞分化。微阵列分析证实了这些发现，并揭示了属于AP-1、MAF、PPAR和MiT家族的巨噬细胞相关转录因子的上调。总之，我们的数据表明MafB是人类单核细胞生成的关键调节因子。
