title: The sexual identity of adult intestinal stem cells controls organ size and plasticity.
abstract: Sex differences in physiology and disease susceptibility are commonly attributed to developmental and/or hormonal factors, but there is increasing realization that cell-intrinsic mechanisms play important and persistent roles. Here we use the Drosophila melanogaster intestine to investigate the nature and importance of cellular sex in an adult somatic organ in vivo. We find that the adult intestinal epithelium is a cellular mosaic of different sex differentiation pathways, and displays extensive sex differences in expression of genes with roles in growth and metabolism. Cell-specific reversals of the sexual identity of adult intestinal stem cells uncovers the key role this identity has in controlling organ size, reproductive plasticity and response to genetically induced tumours. Unlike previous examples of sexually dimorphic somatic stem cell activity, the sex differences in intestinal stem cell behaviour arise from intrinsic mechanisms that control cell cycle duration and involve a new doublesex- and fruitless-independent branch of the sex differentiation pathway downstream of transformer. Together, our findings indicate that the plasticity of an adult somatic organ is reversibly controlled by its sexual identity, imparted by a new mechanism that may be active in more tissues than previously recognized.
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Bruno
authors.initials: B
authors.lastname: Hudry
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Khadayate
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Irene
authors.initials: I
authors.lastname: Miguel-Aliaga
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000033:anatomy & histology* / Q000166:cytology* / Q000235:genetics / Q000254:growth & development; D005260:Female; D007422:Intestines / Q000166:cytology*; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D009929:Organ Size; D016601:RNA-Binding Proteins / Q000378:metabolism; D012098:Reproduction; D012261:Ribonucleoproteins / Q000378:metabolism; D012727:Sex Characteristics; D012733:Sex Differentiation / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C067777:Sxl protein, Drosophila; C097162:Tra protein, Drosophila; C066174:tra2 protein, Drosophila