Whole-animal genome-wide RNAi screen identifies networks regulating male germline stem cells in Drosophila

Ying Liu, Qinglan Ge, Brian Chan, Hanhan Liu, Shree Ram Singh, Jacob Manley, Jae Lee, Ann Marie Weideman, Gerald Hou and Steven X. Hou ()
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Ying Liu: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health
Qinglan Ge: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health
Brian Chan: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health
Hanhan Liu: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health
Shree Ram Singh: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health
Jacob Manley: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health
Jae Lee: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health
Ann Marie Weideman: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health
Gerald Hou: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health
Steven X. Hou: Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12149

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