De?ning gene networks controlling the maintenance and function of the differentiation niche by an in vivo systematic RNAi screen
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摘要
In the Drosophila ovary, escort cells (ECs) extrinsically control germline stem cell (GSC) maintenance and progeny differentiation. However, the underlying mechanisms remain poorly understood. In this study,we identified 173 EC genes for their roles in controlling GSC maintenance and progeny differentiation by using an in vivo systematic RNAi approach. Of the identified genes, 10 and 163 are required in ECs to promote GSC maintenance and progeny differentiation, respectively. The genes required for progeny differentiation fall into different functional categories, including transcription, mRNA splicing, protein degradation, signal transduction and cytoskeleton regulation. In addition, the GSC progeny differentiation defects caused by defective ECs are often associated with BMP signaling elevation, indicating that preventing BMP signaling is a general functional feature of the differentiation niche. Lastly, exon junction complex (EJC) components, which are essential for mRNA splicing, are required in ECs to promote GSC progeny differentiation by maintaining ECs and preventing BMP signaling. Therefore, this study has identified the major regulators of the differentiation niche, which provides important insights into how stem cell progeny differentiation is extrinsically controlled.
In the Drosophila ovary, escort cells (ECs) extrinsically control germline stem cell (GSC) maintenance and progeny differentiation. However, the underlying mechanisms remain poorly understood. In this study,we identified 173 EC genes for their roles in controlling GSC maintenance and progeny differentiation by using an in vivo systematic RNAi approach. Of the identified genes, 10 and 163 are required in ECs to promote GSC maintenance and progeny differentiation, respectively. The genes required for progeny differentiation fall into different functional categories, including transcription, mRNA splicing, protein degradation, signal transduction and cytoskeleton regulation. In addition, the GSC progeny differentiation defects caused by defective ECs are often associated with BMP signaling elevation, indicating that preventing BMP signaling is a general functional feature of the differentiation niche. Lastly, exon junction complex (EJC) components, which are essential for mRNA splicing, are required in ECs to promote GSC progeny differentiation by maintaining ECs and preventing BMP signaling. Therefore, this study has identified the major regulators of the differentiation niche, which provides important insights into how stem cell progeny differentiation is extrinsically controlled.
In the Drosophila ovary, escort cells (ECs) extrinsically control germline stem cell (GSC) maintenance and progeny differentiation. However, the underlying mechanisms remain poorly understood. In this study,we identified 173 EC genes for their roles in controlling GSC maintenance and progeny differentiation by using an in vivo systematic RNAi approach. Of the identified genes, 10 and 163 are required in ECs to promote GSC maintenance and progeny differentiation, respectively. The genes required for progeny differentiation fall into different functional categories, including transcription, mRNA splicing, protein degradation, signal transduction and cytoskeleton regulation. In addition, the GSC progeny differentiation defects caused by defective ECs are often associated with BMP signaling elevation, indicating that preventing BMP signaling is a general functional feature of the differentiation niche. Lastly, exon junction complex (EJC) components, which are essential for mRNA splicing, are required in ECs to promote GSC progeny differentiation by maintaining ECs and preventing BMP signaling. Therefore, this study has identified the major regulators of the differentiation niche, which provides important insights into how stem cell progeny differentiation is extrinsically controlled.
引文
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Kai,T.S.,Spradling,A.,2003.An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells.Proc.Natl.Acad.Sci.U.S.A.100,4633e4638.
Kirilly,D.,Wang,S.,Xie,T.,2011.Self-maintained escort cells form a germline stem cell differentiation niche.Development 138,5087e5097.
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Li,L.H.,Xie,T.,2005.Stem cell niche:structure and function.Annu.Rev.Cell Dev.Biol.21,605e631.
Li,X.W.,Yang,F.,Chen,H.Y.,Deng,B.W.,Li,X.H.,Xi,R.W.,2016.Control of germline stem cell differentiation by Polycomb and Trithorax group genes in the niche microenvironment.Development 143,3449e3458.
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Li,Y.,Zhang,Q.,Carreira-Rosario,A.,Maines,J.Z.,McKearin,D.M.,Buszczak,M.,2013.Mei-P26 cooperates with bam,Bgcn and Sxl to promote early germline development in the Drosophila ovary.PLoS One 8,e58301.
Lin,H.,Spradling,A.C.,1993.Germline stem-cell division and egg chamber development in transplanted Drosophila germaria.Dev.Biol.159,140e152.
Lin,H.,Yue,L.,Spradling,A.C.,1994.The Drosophila fusome,a germline-specific organelle,contains membrane skeletal proteins and functions in cyst formation.Development 120,947e956.
Liu,M.,Lim,T.M.,Cai,Y.,2010.The Drosophila female germline stem cell lineage acts to spatially restrict DPP function within the niche.Sci.Signal.3,ra57.
Liu,Z.,Zhong,G.H.,Chai,P.C.,Luo,L.C.,Liu,S.,Yang,Y.,Baeg,G.H.,Cai,Y.,2015.Coordinated niche-associated signals promote germline homeostasis in the Drosophila ovary.J.Cell Biol.211,469e484.
Lu,T.L.,Wang,S.,Gao,Y.,Mao,Y.,Yang,Z.H.,Liu,L.P.,Song,X.Q.,Ni,J.Q.,Xie,T.,2015.COP9-Hedgehog axis regulates the function of the germline stem cell progeny differentiation niche in the Drosophila ovary.Development 142,4242e4252.
Luo,L.C.,Wang,H.S.,Fan,C.,Liu,S.,Cai,Y.,2015.Wnt ligands regulate Tkv expression to constrain Dpp activity in the Drosophila ovarian stem cell niche.J.Cell Biol.209,595e608.
Ma,X.,Wang,S.,Do,T.,Song,X.Q.,Inaba,M.,Nishimoto,Y.,Liu,L.P.,Gao,Y.,Mao,Y.,Li,H.,McDowell,W.,Park,J.,Malanowski,K.,Peak,A.,Perera,A.,Li,H.,Gaudenz,K.,Haug,J.,Yamashita,Y.,Lin,H.F.,Ni,J.Q.,Xie,T.,2014.Piwi is required in multiple cell types to control germline stem cell lineage development in the Drosophila ovary.PLoS One 9,e90267.
Maimon,I.,Popliker,M.,Gilboa,L.,2014.Without children is required for Statmediated zfh1 transcription and for germline stem cell differentiation.Development 141,2602e2610.
Malone,C.D.,Mestdagh,C.,Akhtar,J.,Kreim,N.,Deinhard,P.,Sachidanandam,R.,Treisman,J.,Roignant,J.Y.,2014.The exon junction complex controls transposable element activity by ensuring faithful splicing of the piwi transcript.Genes Dev.28,1786e1799.
Margolis,J.,Spradling,A.,1995.Identification and behavior of epithelial stem cells in the Drosophila ovary.Development 121,3797e3807.
McKearin,D.,Ohlstein,B.,1995.A role for the Drosophila bag-of-marbles protein in the differentiation of cystoblasts from germline stem cells.Development 121,2937e2947.
McKearin,D.M.,Spradling,A.C.,1990.bag-of-marbles:a Drosophila gene required to initiate both male and female gametogenesis.Genes Dev.4,2242e2251.
Morris,L.X.,Spradling,A.C.,2011.Long-term live imaging provides new insight into stem cell regulation and germline-soma coordination in the Drosophila ovary.Development 138,2207e2215.
Morris,L.X.,Spradling,A.C.,2012.Steroid signaling within Drosophila ovarian epithelial cells sex-specifically modulates early germ cell development and meiotic entry.PLoS One 7,e46109.
Morrison,S.J.,Spradling,A.C.,2008.Stem cells and niches:mechanisms that promote stem cell maintenance throughout life.Cell 132,598e611.
Mottier-Pavie,V.I.,Palacios,V.,Eliazer,S.,Scoggin,S.,Buszczak,M.,2016.The Wnt pathway limits BMP signaling outside of the germline stem cell niche in Drosophila ovaries.Dev.Biol.417,50e62.
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