Polycomb Group Genes Psc and Su(z)2 Maintain Somatic Stem Cell Identity and Activity in Drosophila

Abstract

Adult stem cells are essential for the proper function of many tissues, yet the mechanisms that maintain the proper identity and regulate proliferative capacity in stem cell lineages are not well understood. Polycomb group (PcG) proteins are transcriptional repressors that have recently emerged as important regulators of stem cell maintenance and differentiation. Here we describe the role of Polycomb Repressive Complex 1 (PRC1) genes Posterior sex combs (Psc) and Suppressor of zeste two (Su(z)2) in restricting the proliferation and maintaining the identity of the Cyst Stem Cell (CySC) lineage in the Drosophila testis. In contrast, Psc and Su(z)2 seem to be dispensable for both germline stem cell (GSC) maintenance and germ cell development. We show that loss of Psc and Su(z)2 function in the CySC lineage results in the formation of aggregates of mutant cells that proliferate abnormally, and display abnormal somatic identity correlated with derepression of the Hox gene Abdominal-B. Furthermore, we show that tumorigenesis in the CySC lineage interferes non-cell autonomously with maintenance of GSCs most likely by displacing them from their niche.

BMI1 represses Ink4a/Arf and Hox genes to regulate stem cells in the rodent incisor

“…We found that the second function of BMI1 is to suppress the expression of Hox genes to prevent inappropriate cell differentiation. A similar observation was made in the Drosophila testis, where mutated polycomb genes resulted in Abdominal-B upregulation and abnormal cyst stem cell differentiation 30 , hinting at an evolutionarily conserved role for Bmi1 in regulating stem cell differentiation. It is notable that upregulation of Hox genes has also been documented in other Bmi1 −/− adult stem cells 1, 2, 5–7 , and it will be important to consider the role of repression of Hox genes and other targets by BMI1 in those systems.…”

Persistent Replicative Stress Alters Polycomb Phenotypes and Tissue Homeostasis in Drosophila melanogaster

“…Elegant experiments by Chen et al demonstrated that several PRC1 components are recruited to the nucleolus in spermatocytes upon terminal differentiation, suggesting that PcG activity may be required in early germ cells to repress the expression of differentiation genes (Chen et al, 2005). Interestingly, loss of the Drosophila PRC1 members Psc [Mel18] and Su(z)2 [Bmi1] in germ cells did not result in loss of GSCs (Morillo Prado et al, 2012), which may suggest a different PRC1 composition in male germ cells. Moreover, the mammalian homolog of Mxc, NPAT, plays a role in DNA repair by regulating the expression of ATM (Ataxia telangiectasia mutated), in addition to H2 and H4 (Medina et al, 2007; White et al, 2011).…”

Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes

“…dpp -LHG and lexO-mCherry-CAAX , from K. Basler ( Yagi et al., 2010 ); UAS-ILK:GFP , from N. Brown ( Zervas et al., 2001 ); UAS-mysRNAi and UAS-mewRNAi ( Han et al, 2012 ); FRT42D Vang 6 , from M. Mlodzik ( Wu and Mlodzik, 2008 ); hs-FLP; FRT2A GFP , from M. Buszczak. hs-FLP; FRT42D GFP , from M. Fuller ( Morillo Prado et al., 2012 ); lexO-CD4-GFP 11 and UAS-CD4-GFP 1–10 , from K. Scott; dpp -Gal4/CyO and btl -Gal4 ( Sato and Kornberg, 2002 ); dad-GFP ( Ninov et al, 2010 ); UAS-pkRNAi , from S. Eaton; dally 80 , dlp A187 and UAS-dallyRNAi (II and III), from H. Nakato ( Akiyama et al, 2008 ); dally-GFP (Kyoto Stock Center); UAS-VangRNAi from the Vienna Drosophila RNAi Center; pk 13 (pk pk-sple13 ), Vang 153 (Vang stbm-153 ), ft 8 , ds UAO71 , ap -Gal4, UAS-ifRNAi and UAS-dlpRNAi from the Bloomington Stock Center.…”