Genome-wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in Drosophila

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 Drosop...

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Main Authors: Xiankun Zeng, Lili Han, Shree Ram Singh, Hanhan Liu, Ralph A. Neumüller, Dong Yan, Yanhui Hu, Ying Liu, Wei Liu, Xinhua Lin, Steven X. Hou
Format: Article
Language:English
Published: Elsevier 2015-02-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124715000765
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author Xiankun Zeng
Lili Han
Shree Ram Singh
Hanhan Liu
Ralph A. Neumüller
Dong Yan
Yanhui Hu
Ying Liu
Wei Liu
Xinhua Lin
Steven X. Hou
author_facet Xiankun Zeng
Lili Han
Shree Ram Singh
Hanhan Liu
Ralph A. Neumüller
Dong Yan
Yanhui Hu
Ying Liu
Wei Liu
Xinhua Lin
Steven X. Hou
author_sort Xiankun Zeng
collection DOAJ
description 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.
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spelling doaj.art-1720ca25838943eab920d8d071602ed82022-12-21T18:57:32ZengElsevierCell Reports2211-12472015-02-011071226123810.1016/j.celrep.2015.01.051Genome-wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in DrosophilaXiankun Zeng0Lili Han1Shree Ram Singh2Hanhan Liu3Ralph A. Neumüller4Dong Yan5Yanhui Hu6Ying Liu7Wei Liu8Xinhua Lin9Steven X. Hou10Basic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USAKey Laboratory of Stem Cell and Developmental Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100864, ChinaBasic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USABasic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USADepartment of Genetics, Harvard Medical School, Boston, MA 02115, USADepartment of Genetics, Harvard Medical School, Boston, MA 02115, USADepartment of Genetics, Harvard Medical School, Boston, MA 02115, USABasic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USABasic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USAKey Laboratory of Stem Cell and Developmental Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100864, ChinaBasic Research Laboratory, National Cancer Institute at Frederick, NIH, Frederick, MD 21702, USAThe 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.http://www.sciencedirect.com/science/article/pii/S2211124715000765
spellingShingle Xiankun Zeng
Lili Han
Shree Ram Singh
Hanhan Liu
Ralph A. Neumüller
Dong Yan
Yanhui Hu
Ying Liu
Wei Liu
Xinhua Lin
Steven X. Hou
Genome-wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in Drosophila
Cell Reports
title Genome-wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in Drosophila
title_full Genome-wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in Drosophila
title_fullStr Genome-wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in Drosophila
title_full_unstemmed Genome-wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in Drosophila
title_short Genome-wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in Drosophila
title_sort genome wide rnai screen identifies networks involved in intestinal stem cell regulation in drosophila
url http://www.sciencedirect.com/science/article/pii/S2211124715000765
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