A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal

Abstract

Germ-line stem cells (GSCs) serve as the source for gametogenesis in diverse organisms. We cloned and characterized the Drosophila piwi gene and showed that it is required for the asymmetric division of GSCs to produce and maintain a daughter GSC but is not essential for the further differentiation of the committed daughter cell. Genetic mosaic and RNA in situ analyses suggest that piwi expression in adjacent somatic cells regulates GSC division. piwi encodes a highly basic novel protein, well conserved during evolution. We isolated piwi homologs in Caenorhabditis elegans and humans and also identified Arabidopsis piwi-like genes known to be required for meristem cell maintenance. Decreasing C. elegans piwi expression reduces the proliferation of GSC-equivalent cells. Thus, piwi represents a novel class of genes required for GSC division in diverse organisms.

Genetic dissection of a stem cell niche: The case of the Drosophila ovary

“…A member of the Argonaute family of RNA binding proteins, piwi is expressed in both somatic and germline cells, and is required within the soma for the maintenance of GSCs (Cox et al, 1998(Cox et al, , 2000. Somatic overexpression of piwi causes a reversible increase in the number of anterior GSC-like germ cells (Cox et al, 2000;King et al, 2001).…”

Buthionine sulfoximine (BSO)-mediated improvement in cultured embryo quality in vitro entails changes in ascorbate metabolism, meristem development and embryo maturation

“…The ARGONAUTE family are large proteins characterized by conserved PAZ and PIWI domains that are thought to be important for protein-protein interaction (Cerrutti et al 2000). AGO proteins, in addition to their well characterized role in RNA interference (reviewed by Carmell et al 2002), have been shown to regulate stem cell identity and cell fate decision in both animal and plant systems (Bohmert et al 1998;Moussian et al 1998;Cox et al 1998;Kataoka et al 2001). Genetic analyses suggest that AGO1 is required for both meristem formation and identity (Lynn et al 1999;Kidner and Martienssen 2005), as in ago1 mutant plants the shoot apical meristem is often replaced by a pin-like organ (Lynn et al 1999).…”

Epigenetics and the plasticity of differentiation in normal and cancer stem cells

“…Regarding the CT genes, expression of MAGEA1, MAGEA2 and MAGEA3 increased cancer cell resistance to tumor necrosis factor and expression of MAGEA2 or MAGEA6 increased resistance to chemotherapeutic compounds (Simpson et al, 2005). Piwi2, another testis gene (Sasaki et al, 2003) that is essential for normal spermatogenesis (Deng and Lin, 2002), plays an important role in the self-renewal of spermatogenic stem cells (Cox et al, 1998). Piwi2 is expressed in many tumors, thus qualifying as a CT gene, and this gene can upregulate expression of the antiapoptotic protein BclxL through activation of STAT3, thus inhibiting apoptosis and promoting growth of the tumor cells (Lee et al, 2006a).…”