Regulation of Ribosome Biogenesis and Protein Synthesis Controls Germline Stem Cell Differentiation

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2015 Dec 17

PMID 26669894

Citations 118

Authors

Carlos G Sanchez

Felipe Karam Teixeira

Benjamin Czech

Jonathan B Preall

Andrea L Zamparini

Jessica R K Seifert

Colin D Malone

Gregory J Hannon

Ruth Lehmann

Affiliations

Soon will be listed here.

Abstract

Complex regulatory networks regulate stem cell behavior and contributions to tissue growth, repair, and homeostasis. A full understanding of the networks controlling stem cell self-renewal and differentiation, however, has not yet been realized. To systematically dissect these networks and identify their components, we performed an unbiased, transcriptome-wide in vivo RNAi screen in female Drosophila germline stem cells (GSCs). Based on characterized cellular defects, we classified 646 identified genes into phenotypic and functional groups and unveiled a comprehensive set of networks regulating GSC maintenance, survival, and differentiation. This analysis revealed an unexpected role for ribosomal assembly factors in controlling stem cell cytokinesis. Moreover, our data show that the transition from self-renewal to differentiation relies on enhanced ribosome biogenesis accompanied by increased protein synthesis. Collectively, these results detail the extensive genetic networks that control stem cell homeostasis and highlight the intricate regulation of protein synthesis during differentiation.

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References

Ni J, Zhou R, Czech B, Liu L, Holderbaum L, Yang-Zhou D . A genome-scale shRNA resource for transgenic RNAi in Drosophila. Nat Methods. 2011; 8(5):405-7. PMC: 3489273. DOI: 10.1038/nmeth.1592. View

Kai T, Spradling A . An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells. Proc Natl Acad Sci U S A. 2003; 100(8):4633-8. PMC: 153607. DOI: 10.1073/pnas.0830856100. View

Glatter T, Schittenhelm R, Rinner O, Roguska K, Wepf A, Junger M . Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome. Mol Syst Biol. 2011; 7:547. PMC: 3261712. DOI: 10.1038/msb.2011.79. View

Ingolia N, Lareau L, Weissman J . Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell. 2011; 147(4):789-802. PMC: 3225288. DOI: 10.1016/j.cell.2011.10.002. View

Chen D, McKearin D . A discrete transcriptional silencer in the bam gene determines asymmetric division of the Drosophila germline stem cell. Development. 2003; 130(6):1159-70. DOI: 10.1242/dev.00325. View

Buszczak M, Signer R, Morrison S . Cellular differences in protein synthesis regulate tissue homeostasis. Cell. 2014; 159(2):242-51. PMC: 4222182. DOI: 10.1016/j.cell.2014.09.016. View

Chen D, McKearin D . Dpp signaling silences bam transcription directly to establish asymmetric divisions of germline stem cells. Curr Biol. 2003; 13(20):1786-91. DOI: 10.1016/j.cub.2003.09.033. View

Cooley L, Kelley R, Spradling A . Insertional mutagenesis of the Drosophila genome with single P elements. Science. 1988; 239(4844):1121-8. DOI: 10.1126/science.2830671. View

McKearin D, Spradling A . bag-of-marbles: a Drosophila gene required to initiate both male and female gametogenesis. Genes Dev. 1990; 4(12B):2242-51. DOI: 10.1101/gad.4.12b.2242. View

10.

Schupbach T, Wieschaus E . Female sterile mutations on the second chromosome of Drosophila melanogaster. II. Mutations blocking oogenesis or altering egg morphology. Genetics. 1991; 129(4):1119-36. PMC: 1204776. DOI: 10.1093/genetics/129.4.1119. View

11.

Robinson D, Cant K, Cooley L . Morphogenesis of Drosophila ovarian ring canals. Development. 1994; 120(7):2015-25. DOI: 10.1242/dev.120.7.2015. View

12.

Lin H, Yue L, Spradling A . The Drosophila fusome, a germline-specific organelle, contains membrane skeletal proteins and functions in cyst formation. Development. 1994; 120(4):947-56. DOI: 10.1242/dev.120.4.947. View

13.

Perrimon N, Lanjuin A, Arnold C, Noll E . Zygotic lethal mutations with maternal effect phenotypes in Drosophila melanogaster. II. Loci on the second and third chromosomes identified by P-element-induced mutations. Genetics. 1996; 144(4):1681-92. PMC: 1207719. DOI: 10.1093/genetics/144.4.1681. View

14.

Tsuneizumi K, Nakayama T, Kamoshida Y, Kornberg T, Christian J, Tabata T . Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature. 1997; 389(6651):627-31. DOI: 10.1038/39362. View

15.

Eikenes A, Malerod L, Christensen A, Steen C, Mathieu J, Nezis I . ALIX and ESCRT-III coordinately control cytokinetic abscission during germline stem cell division in vivo. PLoS Genet. 2015; 11(1):e1004904. PMC: 4312039. DOI: 10.1371/journal.pgen.1004904. View

16.

Matias N, Mathieu J, Huynh J . Abscission is regulated by the ESCRT-III protein shrub in Drosophila germline stem cells. PLoS Genet. 2015; 11(2):e1004653. PMC: 4372032. DOI: 10.1371/journal.pgen.1004653. View

17.

Truitt M, Conn C, Shi Z, Pang X, Tokuyasu T, Coady A . Differential Requirements for eIF4E Dose in Normal Development and Cancer. Cell. 2015; 162(1):59-71. PMC: 4491046. DOI: 10.1016/j.cell.2015.05.049. View

18.

Barrett K, Leptin M, Settleman J . The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation. Cell. 1998; 91(7):905-15. DOI: 10.1016/s0092-8674(00)80482-1. View

19.

de Cuevas M, Spradling A . Morphogenesis of the Drosophila fusome and its implications for oocyte specification. Development. 1998; 125(15):2781-9. DOI: 10.1242/dev.125.15.2781. View

20.

McMahon S, Van Buskirk H, Dugan K, Copeland T, Cole M . The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins. Cell. 1998; 94(3):363-74. DOI: 10.1016/s0092-8674(00)81479-8. View