Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi
Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi
复制标题
DOI：
10.1182/blood.v97.2.426
复制
发表时间：
2001-01-15
期刊：
影响因子：
20.3
通讯作者：
Hoffman, R
中科院分区：
文献类型：
--
作者：
Sharma, AK;Nelson, MC;Hoffman, R
造血干细胞(HSCs)具有向多种造血细胞分化或自我更新的双重能力。这些特性的分子基础尚不清楚，最近在果蝇胚胎生殖系干细胞(GSCs)中发现了piwi基因，并被证明在GSC自我更新中具有重要作用。本研究表明，hiwi基因是一种新的人类Piwi同源物，也存在于人CD34(+)造血祖细胞中，而不是在分化较多的细胞群中。将CD34(+)细胞置于支持分化和快速退出干细胞室的培养条件下，会导致在14天培养期间的第5天失去hiwi的表达。在许多发育中的胎儿和成人组织中都检测到了hiwi基因的表达。通过5‘RACE克隆方法，从人CD34(+)骨髓细胞中克隆了一个新的全长Hiwi互补DNA。在氨基酸水平上，人HIWI蛋白与果蝇蛋白有52%的同源性。Hiwi在人白血病细胞系KG1中的瞬时表达导致细胞增殖显著降低。Annexin V检测系统显示，hiwi过表达导致KG1细胞程序性死亡。这些研究表明，hiwi可能是一种重要的负向发育调节因子，这在一定程度上是与造血干细胞和造血祖细胞相关的独特生物学特性的基础。(C)2001年，由美国血液病学会提供。
Hematopoietic stem cells (HSCs) are characterized by their dual abilities to undergo differentiation into multiple hematopoietic cell lineages or to undergo self-renewal. The molecular basis of these properties remains poorly understood, Recently the piwi gene was found in the embryonic germline stem cells (GSCs) of Drosophila melanogaster and has been shown to be important in GSC self-renewal, This study demonstrated that hiwi, a novel human homologue of piwi, is also present in human CD34(+) hematopoietic progenitor cells bat not in more differentiated cell populations. Placing CD34(+) cells into culture conditions that supported differentiation and rapid exit from the stem cell compartment resulted in a loss of hiwi expression by day 5 of a 14-day culture period. Expression of the hiwi gene was detected in many developing fetal and adult tissues. By means of 5' RACE cloning methodology, a novel putative full-length hiwi complementary DNA was cloned from human CD34(+) marrow cells. At the amino acid level, the human HIWI protein was 52% homologous to the Drosophila protein. The transient expression of hiwi in the human leukemia cell line KG1 resulted in a dramatic reduction in cellular proliferation. Overexpression of hiwi led to programmed cell death of KG1 cells as demonstrated by the Annexin V assay system. These studies suggest that hiwi maybe an important negative developmental regulator, which, in part, underlies the unique biologic properties associated with hematopoietic stem and progenitor cells. (C) 2001 by The American Society of Hematology.