Olson M C, Scott E W, Hack A A, Su G H, Tenen D G, Singh H, Simon M C
Howard Hughes Medical Institute, University of Chicago, Illinois 60637, USA.
Immunity. 1995 Dec;3(6):703-14. doi: 10.1016/1074-7613(95)90060-8.
We have previously shown using gene targeting that PU.1 is essential for the development of lymphoid and myeloid lineages during fetal liver hematopoiesis. We now show that PU.1 is required for the maturation of yolk sac-derived myeloid progenitors and for the differentiation of ES cells into macrophages. The role of PU.1 in regulating target genes, thought to be critical in the development of monocytes and granulocytes, has been analyzed. Early genes such as GM-CSFR, G-CSFR, and myeloperoxidase are expressed in PU.1-/- embryos and differentiated PU.1-/- ES cells. However, the expression of genes associated with terminal myeloid differentiation (CD11b, CD64, and M-CSFR) is eliminated in differentiated PU.1-/- ES cells. Development of macrophages is restored with the introduction of a PU.1 cDNA regulated by its own promoter. The PU.1-/- ES cells represent an important model for analyzing myeloid cell development.
我们之前利用基因靶向技术表明，PU.1在胎儿肝脏造血过程中对淋巴样和髓样谱系的发育至关重要。我们现在表明，PU.1是卵黄囊来源的髓样祖细胞成熟以及ES细胞分化为巨噬细胞所必需的。PU.1在调控靶基因中的作用已被分析，这些靶基因被认为在单核细胞和粒细胞的发育中至关重要。早期基因如GM-CSFR、G-CSFR和髓过氧化物酶在PU.1基因敲除胚胎和分化的PU.1基因敲除ES细胞中表达。然而，与终末髓样分化相关的基因（CD11b、CD64和M-CSFR）的表达在分化的PU.1基因敲除ES细胞中被消除。通过引入由其自身启动子调控的PU.1 cDNA，巨噬细胞的发育得以恢复。PU.1基因敲除ES细胞是分析髓样细胞发育的重要模型。
