title: Histone H1 defect in escort cells triggers germline tumor in Drosophila ovary.
abstract: Drosophila ovary is recognized as one of the best model systems to study stem cell biology in vivo. We had previously identified an autonomous role of the histone H1 in germline stem cell (GSC) maintenance. Here, we found that histone H1 depletion in escort cells (ECs) resulted in an increase of spectrosome-containing cells (SCCs), an ovary tumor-like phenotype. Further analysis showed that the Dpp pathway is excessively activated in these SCC cells, while the expression of bam is attenuated. In the H1-depleted ECs, both transposon activity and DNA damage had increased dramatically, followed by EC apoptosis, which is consistent with the role of H1 in other somatic cells. Surprisingly, H1-depleted ECs acquired cap cell characteristics including dpp expression, and the resulting abnormal Dpp level inhibits SCC further differentiation. Most interestingly, double knockdown of H1 and dpp in ECs can reduce the number of SCCs to the normal level, indicating that the additional Dpp secreted by ECs contributes to the germline tumor. Taken together, our findings indicate that histone H1 is an important epigenetic factor in controlling EC characteristics and a key suppressor of germline tumor.
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yuzhao
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Qiao
authors.affiliation: COFCO Nutrition and Health Research Institute, Beijing 102209, China; College of Bioengineering, Hubei University of Technology, Wuhan 430068, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Xu
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Decai
authors.initials: D
authors.lastname: Mao
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xingjie
authors.initials: X
authors.lastname: Ren
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Pan
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Rong-Gang
authors.initials: RG
authors.lastname: Xu
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Bo-Wen
authors.initials: BW
authors.lastname: Xu
authors.affiliation: Department of Biology, University of California, San Diego, USA.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: French International School of Hong Kong, Hong Kong.
authors.forename: Haiyi
authors.initials: H
authors.lastname: Li
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Miao
authors.affiliation: Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Hu
authors.affiliation: School of Medicine, Institute of Biomedicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
authors.affiliation: School of Medicine, Institute of Biomedicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Basic Medical Sciences, Center for Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zai
authors.initials: Z
authors.lastname: Chang
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua Fly Center, Tsinghua University, Beijing 100084, China.
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Qingfei
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: nijq@mail.tsinghua.edu.cn.
authors.forename: Jian-Quan
authors.initials: JQ
authors.lastname: Ni
mesh_terms: D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D004249:DNA Damage; D004251:DNA Transposable Elements / Q000235:genetics; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D005854:Germ Cells / Q000378:metabolism* / Q000473:pathology*; D006657:Histones / Q000378:metabolism*; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D004251:DNA Transposable Elements; D006657:Histones
keywords: Escort cell; Histone H1; Niche; Stem cell