title: Genome-wide RNAi screen identifies networks involved in intestinal stem cell regulation in Drosophila.
abstract: The intestinal epithelium is the most rapidly self-renewing tissue in adult animals and maintained by intestinal stem cells (ISCs) in both Drosophila and mammals. To comprehensively identify genes and pathways that regulate ISC fates, we performed a genome-wide transgenic RNAi screen in adult Drosophila intestine and identified 405 genes that regulate ISC maintenance and lineage-specific differentiation. By integrating these genes into publicly available interaction databases, we further developed functional networks that regulate ISC self-renewal, ISC proliferation, ISC maintenance of diploid status, ISC survival, ISC-to-enterocyte (EC) lineage differentiation, and ISC-to-enteroendocrine (EE) lineage differentiation. By comparing regulators among ISCs, female germline stem cells, and neural stem cells, we found that factors related to basic stem cell cellular processes are commonly required in all stem cells, and stem-cell-specific, niche-related signals are required only in the unique stem cell type. Our findings provide valuable insights into stem cell maintenance and lineage-specific differentiation.
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: Xiankun
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Stem Cell and Developmental Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100864, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Han
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: Shree Ram
authors.initials: SR
authors.lastname: Singh
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: Hanhan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität, Feodor-Lynen-Strasse 25, 81377 München, Germany.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Neumüller
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Stem Cell and Developmental Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100864, China; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lin
authors.affiliation: Basic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USA. Electronic address: hous@mail.nih.gov.
authors.forename: Steven X
authors.initials: SX
authors.lastname: Hou
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D016208:Databases, Factual; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D053263:Gene Regulatory Networks; D016678:Genome; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D012330:RNA, Double-Stranded; D018123:Receptors, Interleukin; D050791:STAT Transcription Factors; C105675:Stat92E protein, Drosophila; C444499:dome protein, Drosophila