title: Whole-animal genome-wide RNAi screen identifies networks regulating male germline stem cells in Drosophila.
abstract: Stem cells are regulated both intrinsically and externally, including by signals from the local environment and distant organs. To identify genes and pathways that regulate stem-cell fates in the whole organism, we perform a genome-wide transgenic RNAi screen through ubiquitous gene knockdowns, focusing on regulators of adult Drosophila testis germline stem cells (GSCs). Here we identify 530 genes that regulate GSC maintenance and differentiation. Of these, we further knock down 113 selected genes using cell-type-specific Gal4s and find that more than half were external regulators, that is, from the local microenvironment or more distal sources. Some genes, for example, versatile (vers), encoding a heterochromatin protein, regulates GSC fates differentially in different cell types and through multiple pathways. We also find that mitosis/cytokinesis proteins are especially important for male GSC maintenance. Our findings provide valuable insights and resources for studying stem cell regulation at the organismal level.
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, 1050 Boyles Street, Building 560, Room 12-70, Frederick, Maryland 21702, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, 1050 Boyles Street, Building 560, Room 12-70, Frederick, Maryland 21702, USA.
authors.forename: Qinglan
authors.initials: Q
authors.lastname: Ge
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, 1050 Boyles Street, Building 560, Room 12-70, Frederick, Maryland 21702, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Chan
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, 1050 Boyles Street, Building 560, Room 12-70, Frederick, Maryland 21702, USA.
authors.forename: Hanhan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, 1050 Boyles Street, Building 560, Room 12-70, Frederick, Maryland 21702, USA.
authors.forename: Shree Ram
authors.identifier: 0000-0001-6545-583X
authors.initials: SR
authors.lastname: Singh
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, 1050 Boyles Street, Building 560, Room 12-70, Frederick, Maryland 21702, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Manley
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, 1050 Boyles Street, Building 560, Room 12-70, Frederick, Maryland 21702, USA.
authors.forename: Jae
authors.initials: J
authors.lastname: Lee
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, 1050 Boyles Street, Building 560, Room 12-70, Frederick, Maryland 21702, USA.
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Weideman
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, 1050 Boyles Street, Building 560, Room 12-70, Frederick, Maryland 21702, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hou
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, 1050 Boyles Street, Building 560, Room 12-70, Frederick, Maryland 21702, USA.
authors.forename: Steven X
authors.initials: SX
authors.lastname: Hou
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019070:Cell Lineage; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics*; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D017344:Genes, Insect; D049750:Genome, Insect; D005854:Germ Cells / Q000166:cytology*; D057166:High-Throughput Screening Assays; D008297:Male; D009928:Organ Specificity; D010641:Phenotype; D011485:Protein Binding; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D055153:Stem Cell Niche / Q000235:genetics; D013234:Stem Cells / Q000166:cytology*
chemical_list: D029721:Drosophila Proteins