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Blood, 15 January 2001, Vol. 97, No. 2, pp. 426-434
HEMATOPOIESIS
Human CD34+ stem cells express the hiwi
gene, a human homologue of the Drosophila gene
piwi
Arun K. Sharma,
Mary C. Nelson,
John E. Brandt,
Maija Wessman,
Nadim Mahmud,
Kevin P. Weller, and
Ronald Hoffman
From the Hematology/Oncology Section, Department of
Medicine, University of Illinois at Chicago, Chicago, IL; and the
University of Helsinki, Department of Molecular Genetics, Helsinki,
Finland.
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 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 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.
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