Human CD34(+) stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi

Hematopoietic stem cells (HSCs) are characterized by their dual abilities t o undergo differentiation into multiple hematopoietic cell lineages or to u ndergo self-renewal. The molecular basis of these properties remains poorly understood, Recently the piwi gene was found in the embryonic germline ste m cells (GSCs) of Drosophila melanogaster and has been shown to be importan t in GSC self-renewal, This study demonstrated that hiwi, a novel human hom ologue of piwi, is also present in human CD34(+) hematopoietic progenitor c ells 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 o f 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 methodolog y, a novel putative full-length hiwi complementary DNA was cloned from huma n 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 ce llular proliferation. Overexpression of hiwi led to programmed cell death o f KG1 cells as demonstrated by the Annexin V assay system. These studies su ggest that hiwi maybe an important negative developmental regulator, which, in part, underlies the unique biologic properties associated with hematopo ietic stem and progenitor cells. (C) 2001 by The American Society of Hemato logy.