title: Twin Promotes the Maintenance and Differentiation of Germline Stem Cell Lineage through Modulation of Multiple Pathways.
abstract: The central question in stem cell regulation is how the balance between self-renewal and differentiation is controlled at the molecular level. This study uses germline stem cells (GSCs) in the Drosophila ovary to demonstrate that the Drosophila CCR4 homolog Twin is required intrinsically to promote both GSC self-renewal and progeny differentiation. Twin/CCR4 is one of the two catalytic subunits in the highly conserved CCR4-NOT mRNA deadenylase complex. Twin works within the CCR4-NOT complex to intrinsically maintain GSC self-renewal, at least partly by sustaining E-cadherin-mediated GSC-niche interaction and preventing transposable element-induced DNA damage. It promotes GSC progeny differentiation by forming protein complexes with differentiation factors Bam and Bgcn independently of other CCR4-NOT components. Interestingly, Bam can competitively inhibit the association of Twin with Pop2 in the CCR4-NOT complex. Therefore, this study demonstrates that Twin has important intrinsic roles in promoting GSC self-renewal and progeny differentiation by functioning in different protein complexes.
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Cuiyun
authors.initials: C
authors.lastname: Geng
authors.affiliation: Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai 200032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Weng
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Lamei
authors.initials: L
authors.lastname: Deng
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Luping
authors.initials: L
authors.lastname: Liu
authors.affiliation: Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai 200032, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Ni
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Anatomy and Cell Biology, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. Electronic address: tgx@stowers.org.
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D064200:Cdh1 Proteins / Q000378:metabolism; D002454:Cell Differentiation; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D005260:Female; D005854:Germ Cells / Q000502:physiology; D008297:Male; D008938:Mitosis; D012260:Ribonucleases / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D055153:Stem Cell Niche; D013234:Stem Cells / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D064200:Cdh1 Proteins; D029721:Drosophila Proteins; C091674:bam protein, Drosophila; C577674:fzr protein, Drosophila; C501437:CCR4 protein, Drosophila; D012260:Ribonucleases; C500128:twin protein, Drosophila