NEW YORK (Reuters Health) - Two research groups have discovered that a DNA transcription repressor protein called Plzf is essential for the self-renewal of spermatogonial stem cells. However, the findings may have implications for oncogenesis as well.

The Plzf gene "is the first gene shown to be required in germ cells for stem cell self-renewal in mammals," senior author Dr. Robert E. Braun, from the University of Washington in Seattle, and colleagues note.

To examine the molecular basis for self-renewal of germline stem cells, Dr. Braun's group used mice carrying the luxoid mutation, a mutation that arose in the 1950s and is associated with a male infertility phenotype among other defects.

The authors found that luxoid mutant contained a nonsense mutation in the gene for Plzf, a known transcription factor. Moreover, in undifferentiated spermatogonia, Plzf was found to be co-expressed with Oct4, a key factor needed to maintain the totipotency of stem cells.

In the second study, Dr. Pier Paolo Pandolfi, from Memorial Sloan-Kettering Cancer Center in New York, and colleagues demonstrated similar findings.

An absence of the Plzf gene was associated with a progressive loss of spermatogonia with age, the researchers note. This loss was linked to increased apoptosis and loss of tubule structure, but not with overt differentiation defects or loss of Sertoli cells.

The authors believe that their findings could have implications beyond spermatogenesis. "The ability of Plzf to regulate molecular pathways underlying stem cell maintenance may be perturbed in acute promyelocytic leukemia, thus lending leukemic hemopoietic progenitors a proliferative advantage," they add.

The two reports appear in the May 23rd online issue of Nature Genetics.

Nat Genet 2004;May 23rd online issue:000-000.

Copyright © 2003 Reuters Limited. All rights reserved. Republication or redistribution of Reuters Limited content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters Limited. Reuters Limited shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.