Saunthararajah Yogen, Boccuni Piernicola, Nucifora Giuseppina
Department of Medicine and Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA.
Crit Rev Eukaryot Gene Expr. 2006;16(2):183-92. doi: 10.1615/critreveukargeneexpr.v16.i2.60.
The hematopoietic stem cell (HSC) has the potential to differentiate into mature cells with distinct phenotypes and functions. As suggested in recent reports, this plasticity can expand to include nonhematopoietic lineages, and, indeed, the HSC may repopulate liver and muscle tissues, as well. Considering the flexibility in HSC differentiation, these processes are regulated by a relatively small number of factors, some of which are expressed in all lineages, whereas others are activated only in a specific cell type. Combined evidence from many studies suggests that alternative subsets of these factors work in a combinatorial manner to regulate specific promoters for the induction of a specific lineage. RUNX1 and PU.1 have a fundamental role in HSC differentiation in that multifactor complexes are assembled around these proteins leading to tissue-specific and synergistic gene activation. Here we describe the relationship of RUNX1 with PU.1 as a facet of the combinatorial relationships that determine hematopoietic lineage commitment.
造血干细胞(HSC)具有分化为具有不同表型和功能的成熟细胞的潜力。正如最近的报告所表明的,这种可塑性可以扩展到包括非造血谱系,实际上,造血干细胞也可能重新填充肝脏和肌肉组织。考虑到造血干细胞分化的灵活性,这些过程由相对较少的因子调节,其中一些在所有谱系中表达,而其他一些仅在特定细胞类型中被激活。许多研究的综合证据表明,这些因子的替代亚群以组合方式发挥作用,以调节特定启动子,从而诱导特定谱系。RUNX1和PU.1在造血干细胞分化中具有重要作用,因为多因子复合物围绕这些蛋白质组装,导致组织特异性和协同基因激活。在这里,我们将RUNX1与PU.1的关系描述为决定造血谱系定向的组合关系的一个方面。