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Dev Cell. 2014 Feb 24;28(4):459-73. doi: 10.1016/j.devcel.2014.01.020.

A regulatory network of Drosophila germline stem cell self-renewal.

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  • 1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • 2Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Drosophila RNAi Screening Center, Harvard Medical School, Boston, MA 02115, USA.
  • 3Departments of Genetics and Cell Biology, School of Medicine, Yale University, New Haven, CT 06520, USA.
  • 4Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
  • 5Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address:


Stem cells possess the capacity to generate two cells of distinct fate upon division: one cell retaining stem cell identity and the other cell destined to differentiate. These cell fates are established by cell-type-specific genetic networks. To comprehensively identify components of these networks, we performed a large-scale RNAi screen in Drosophila female germline stem cells (GSCs) covering ∼25% of the genome. The screen identified 366 genes that affect GSC maintenance, differentiation, or other processes involved in oogenesis. Comparison of GSC regulators with neural stem cell self-renewal factors identifies common and cell-type-specific self-renewal genes. Importantly, we identify the histone methyltransferase Set1 as a GSC-specific self-renewal factor. Loss of Set1 in neural stem cells does not affect cell fate decisions, suggesting a differential requirement of H3K4me3 in different stem cell lineages. Altogether, our study provides a resource that will help to further dissect the networks underlying stem cell self-renewal.

Copyright © 2014 Elsevier Inc. All rights reserved.

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