title: Msi2 Maintains Quiescent State of Hair Follicle Stem Cells by Directly Repressing the Hh Signaling Pathway.
abstract: Hair follicles (HFs) undergo precisely regulated cycles of active regeneration (anagen), involution (catagen), and relative quiescence (telogen). Hair follicle stem cells (HFSCs) play important roles in regenerative cycling. Elucidating mechanisms that govern HFSC behavior can help uncover the underlying principles of hair development, hair growth disorders, and skin cancers. RNA-binding proteins of the Musashi (Msi) have been implicated in the biology of different stem cell types, yet they have not been studied in HFSCs. Here we utilized gain- and loss-of-function mouse models to demonstrate that forced MSI2 expression retards anagen entry and consequently delays hair growth, whereas loss of Msi2 enhances hair regrowth. Furthermore, our findings show that Msi2 maintains quiescent state of HFSCs in the process of the telogen-to-anagen transition. At the molecular level, our unbiased transcriptome profiling shows that Msi2 represses Hedgehog signaling activity and that Shh is its direct target in the hair follicle. Taken together, our findings reveal the importance of Msi2 in suppressing hair regeneration and maintaining HFSC quiescence. The previously unreported Msi2-Shh-Gli1 pathway adds to the growing understanding of the complex network governing cyclic hair growth.
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Ma
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Song
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Jiuzhi
authors.initials: J
authors.lastname: Xu
authors.affiliation: Medical Research Center, Department of Radiation Oncology, Peking University Third Hospital, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xiong
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xu
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Physics and State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, Xiamen University, Xiamen, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Shuai
authors.affiliation: Department of Animal Science, Southwest University, Rongchang, Chongqing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research, Center for Complex Biological Systems, University of California, Irvine, Irvine, California, USA.
authors.forename: Maksim V
authors.initials: MV
authors.lastname: Plikus
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, and Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, Philadelphia, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lengner
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China. Electronic address: renfazheng@263.net.
authors.forename: Fazheng
authors.initials: F
authors.lastname: Ren
authors.affiliation: Medical Research Center, Department of Radiation Oncology, Peking University Third Hospital, Beijing, China. Electronic address: lixiangxue@bjmu.edu.cn.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Xue
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China. Electronic address: zyu@cau.edu.cn.
authors.forename: Zhengquan
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006197:Hair / Q000254:growth & development*; D018859:Hair Follicle / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016601:RNA-Binding Proteins / Q000235:genetics*; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; C499059:Msi2h protein, mouse; D016601:RNA-Binding Proteins; C465570:Shh protein, mouse