Differential expression of Hox, Meis1, and Pbx1 genes in primitive cells throughout murine hematopoietic ontogeny
Differential expression of Hox, Meis1, and Pbx1 genes in primitive cells throughout murine hematopoietic ontogeny
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DOI：
10.1016/s0301-472x(01)00757-3
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发表时间：
2002-01-01
影响因子：
2.6
通讯作者：
Humphries, RK
中科院分区：
文献类型：
--
作者：
Pineault, N;Helgason, CD;Humphries, RK
目标。Hox基因转录因子家族被认为参与了原始造血细胞的调节，包括干细胞和早期承诺的祖细胞，也直接与白血病有关。为了进一步了解HOX基因介导的造血调控，我们研究了具有代表性的HOX基因及其两个辅助因子Pbx1和Meis1在小鼠造血不同阶段的表达模式。用流式细胞仪分离小鼠骨髓(BM)和胎肝14.5天(FL)功能不同的细胞亚群，并用全局cDNA扩增技术检测各种同源异型盒基因的表达。HOX基因在造血干细胞(HSC)丰富的亚群中优先表达，在分化和成熟过程中表达下调。这种表达模式在成人和胎儿的造血期都能观察到。Pbx1和Meis1基因在表达模式上有重要差异，但都在Hox表达亚群中检测到。特别是，Meis1一直显示出与Hox基因非常相似的表达谱。最后，利用胚胎干细胞体外分化模型模拟胚胎造血，发现HOX基因及其辅助因子的共表达与造血祖细胞的出现相吻合。综上所述，这些结果进一步支持了HOX基因参与早期造血细胞调控的观点，并提供了强有力的证据，表明它们参与了个体发育过程中的造血调控。(C)2002年国际实验血液学学会。爱思唯尔科学公司出版。
Objective. The Hox gene family of transcription factors is thought to be involved in the regulation of primitive hematopoietic cells, including stem cells and early committed progenitors, and has also been directly implicated in leukemia. To gain further insight into Hox gene-mediated regulation of hematopoiesis, we investigated the expression pattern of representative Hox genes and two of their cofactors, Pbx1 and Meis1, at different stages of murine hematopoiesisMethods. Functionally distinct subpopulations of murine bone marrow (BM) and fetal liver day 14.5 (FL) cells were isolated by flow cytometry, and gene expression of various homeobox-containing genes was assessed by global cDNA amplification technique.Results. Hox genes were found preferentially expressed in hematopoietic stem cell (HSC)-enriched subpopulations and downregulated following differentiation and maturation. This profile of expression was observed at both adult and fetal stages of hematopoiesis. The Pbx1 and Meis1 genes had important differences in their expression pattern but were both detected in Hox expressing subpopulations. In particular, Meis1 consistently showed an expression profile closely resembling that of Hox genes. Finally, using the in vitro embryonic stem (ES) cell differentiation model to mimic embryonic hematopoiesis, we found coexpression of Hox genes and their cofactors coincided with the appearance of hematopoietic progenitor cells.Conclusion. Together, these results further support the notion that Hox genes are involved in the regulation of early hematopoietic cells and provide strong evidence that they are involved in the regulation of hematopoiesis throughout ontogeny. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.