DIFFERENTIAL EXPRESSION OF HOMEOBOX GENES IN FUNCTIONALLY DISTINCT CD34(+) SUBPOPULATIONS OF HUMAN BONE-MARROW CELLS
DIFFERENTIAL EXPRESSION OF HOMEOBOX GENES IN FUNCTIONALLY DISTINCT CD34(+) SUBPOPULATIONS OF HUMAN BONE-MARROW CELLS
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DOI：
10.1073/pnas.91.25.12223
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发表时间：
1994-12-06
影响因子：
11.1
通讯作者：
HUMPHRIES, RK
中科院分区：
文献类型：
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作者：
SAUVAGEAU, G;LANSDORP, PM;HUMPHRIES, RK
一类同源盒（Hox）基因编码一组控制胚胎发育的转录因子，并与造血细胞分化的持续过程有关。它们聚集在四条染色体上，在早期发育中，相对于它们的3‘ - bbb50 ’染色体位置表现出空间限制性表达。通过使用一种改进的基于pcr的方法来扩增来自有限细胞数量的总cDNA，我们现在描述了I类Hox基因在从正常人骨髓中分离的高度纯化的CD34（+）细胞亚群中的表达，这些细胞亚群代表了功能不同的干细胞和祖细胞区室。我们的数据表明，至少有16种不同的Hox基因，主要来自A和B簇，在人类造血细胞的一个或多个亚群中表达。此外，在A和B簇的3‘端发现的一些Hox基因的表达显著升高（例如HoxB3）是包含最原始功能定义细胞的亚群的独特特征，而位于每个簇的5’区域的基因（例如HoxA10）被发现在CD34（+）亚群中表达水平几乎相等。与CD34（+）细胞的结果相反，在骨髓细胞的CD34（-）部分中，两个选定的Hox基因，HoxB3和HoxA10的表达几乎消失。这些结果表明Hox基因在原始造血细胞中广泛表达，并指出在其正常发育过程中存在Hox基因表达调控程序。
Class I homeobox (Hox) genes encode a major group of transcription factors controlling embryonic development and have been implicated in the continuing process of hematopoietic cell differentiation. They are clustered on four chromosomes and, in early development, exhibit spatially restricted expression with respect to their 3' --> 5' chromosomal position. By using an improved PCR-based method for amplifying total cDNA derived from limited cell numbers, we now describe the expression of class I Hox genes in highly purified CD34(+) cell subpopulations isolated from normal human bone marrow that represent functionally distinct stem and progenitor cell compartments. Our data indicate that at least 16 different Hox genes, mainly from the A and the B clusters, are expressed in one or more of these subpopulations of human hematopoietic cells. Moreover, markedly elevated expression of some of the Hox genes found at the 3' end of the A and B clusters (e.g., HoxB3) was a unique feature of the subpopulations that contained the most primitive functionally defined cells, whereas genes located in the 5' region of each cluster (e.g., HoxA10) were found to be expressed at nearly equal levels in the CD34(+) subpopulations analyzed. In contrast to the findings for CD34(+) cells, expression of two selected Hox genes, HoxB3 and HoxA10, was virtually extinguished in the CD34(-)fraction of bone marrow cells. These results demonstrate the expression of a broad range of Hox genes in primitive hematopoietic cells and point to the existence of a regulated program of Hox gene expression during their normal development.