SUMO (Small ubiquitin-related modifier) modification (SUMOylation) is a highly dynamic post-translational modification (PTM) playing important roles in tissue development and disease progression. However, its function in adult stem cell maintenance is largely unknown. Here we report the function of SUMOylation in somatic cyst stem cells (CySCs) self-renewal in adult Drosophila testis. The SUMO pathway cell-autonomously regulates CySCs maintenance. Reduction of SUMOylation promotes premature differentiation of CySCs and impedes the proliferation of CySCs, which finally reduce the number of CySCs. Consistently, CySC clones carrying mutation of the SUMO conjugating enzyme are rapidly lost. Furthermore, inhibition of SUMO pathway phenocopies the disruption of Hedgehog (Hh) pathway, and can block the promoted proliferation of CySCs by Hh activation. Importantly, SUMO pathway directly regulates the SUMOylation of Hh pathway transcriptional factor, Cubitus interruptus (Ci), which is required for promoting CySCs proliferation. Thus, we conclude that SUMO directly targets Hh pathway and regulates CySCs maintenance in adult Drosophila testis.
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RESEARCH REPORT|
01 January 2016
SUMO regulates somatic cyst stem cells maintenance and directly targets hedgehog pathway in adult Drosophila testis
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Stem cells & regeneration
Xiangdong Lv,
Xiangdong Lv
#
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
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Chenyu Pan,
Chenyu Pan
#
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
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Zhao Zhang,
Zhao Zhang
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
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Yuanxin Xia,
Yuanxin Xia
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
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Hao Chen,
Hao Chen
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
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Shuo Zhang,
Shuo Zhang
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
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Tong Guo,
Tong Guo
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
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Hui Han,
Hui Han
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
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Haiyun Song,
Haiyun Song
3
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of sciences, Shanghai 200031, P.R. China
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Lei Zhang,
Lei Zhang
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
2
School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, P.R. China
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Yun Zhao
Yun Zhao
*
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
2
School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, P.R. China
*Author for correspondence: yunzhao@sibcb.ac.cn
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Xiangdong Lv
#
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
Chenyu Pan
#
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
Zhao Zhang
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
Yuanxin Xia
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
Hao Chen
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
Shuo Zhang
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
Tong Guo
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
Hui Han
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
Haiyun Song
3
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of sciences, Shanghai 200031, P.R. China
Lei Zhang
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
2
School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, P.R. China
Yun Zhao
*
1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
2
School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, P.R. China
*Author for correspondence: yunzhao@sibcb.ac.cn
#
These authors contributed equally to this work and are listed alphabetically.
Received:
09 Sep 2015
Accepted:
16 Mar 2016
Online ISSN: 1477-9129
Print ISSN: 0950-1991
© 2016. Published by The Company of Biologists Ltd
2016
Development dev.130773.
Article history
Received:
09 Sep 2015
Accepted:
16 Mar 2016
Currently Viewing Accepted Manuscript - Newer Version Available
15 May 2016
Citation
Xiangdong Lv, Chenyu Pan, Zhao Zhang, Yuanxin Xia, Hao Chen, Shuo Zhang, Tong Guo, Hui Han, Haiyun Song, Lei Zhang, Yun Zhao; SUMO regulates somatic cyst stem cells maintenance and directly targets hedgehog pathway in adult Drosophila testis. Development 2016; dev.130773. doi: https://doi.org/10.1242/dev.130773
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