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Cell Rep. 2015 Feb 24;10(7):1226-38. doi: 10.1016/j.celrep.2015.01.051. Epub 2015 Feb 19.

Genome-wide RNAi screen identifies networks involved in intestinal stem cell regulation in Drosophila.

Author information

1
Basic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USA.
2
Key Laboratory of Stem Cell and Developmental Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100864, China.
3
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.
4
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
5
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.
6
Basic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USA. Electronic address: hous@mail.nih.gov.

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.

PMID:
25704823
PMCID:
PMC4420031
DOI:
10.1016/j.celrep.2015.01.051
[Indexed for MEDLINE]
Free PMC Article

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