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 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.
Sharma
A K
AK
Hematology/Oncology Section, Department of Medicine, University of Illinois at Chicago, 60607, USA.
Nelson
M C
MC
Brandt
J E
JE
Wessman
M
M
Mahmud
N
N
Weller
K P
KP
Hoffman
R
R
D000818:Animals; D018952:Antigens, CD34; D017209:Apoptosis / Q000187:drug effects; D060565:Argonaute Proteins; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004330:Drosophila / Q000737:chemistry; D029721:Drosophila Proteins; D005562:Formazans; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D034743:RNA-Induced Silencing Complex; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013778:Tetrazolium Salts; D014162:Transfection; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34; D060565:Argonaute Proteins; D018076:DNA, Complementary; D029721:Drosophila Proteins; D005562:Formazans; D019476:Insect Proteins; C421088:PIWIL1 protein, human; D011506:Proteins; D034743:RNA-Induced Silencing Complex; D013778:Tetrazolium Salts; C116498:piwi protein, Drosophila; C079782:MTT formazan