Human CD34+ stem cells express the hiwigene, a human homologue of the Drosophila genepiwi

Abstract

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 piwigene was found in the embryonic germline stem cells (GSCs) ofDrosophila 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 but 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 hiwiexpression by day 5 of a 14-day culture period. Expression of thehiwi 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 Drosophilaprotein. 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.