title: Foxp1 Regulates the Proliferation of Hair Follicle Stem Cells in Response to Oxidative Stress during Hair Cycling.
abstract: Hair follicle stem cells (HFSCs) in the bugle circularly generate outer root sheath (ORS) through linear proliferation within limited cycles during anagen phases. However, the mechanisms controlling the pace of HFSC proliferation remain unclear. Here we revealed that Foxp1, a transcriptional factor, was dynamically relocated from the nucleus to the cytoplasm of HFSCs in phase transitions from anagen to catagen, coupled with the rise of oxidative stress. Mass spectrum analyses revealed that the S468 phosphorylation of Foxp1 protein was responsive to oxidative stress and affected its nucleocytoplasmic translocation. Foxp1 deficiency in hair follicles led to compromised ROS accrual and increased HFSC proliferation. And more, NAC treatment profoundly elongated the anagen duration and HFSC proliferation in Foxp1-deficient background. Molecularly, Foxp1 augmented ROS levels through suppression of Trx1-mediated reductive function, thereafter imposing the cell cycle arrest by modulating the activity of p19/p53 pathway. Our findings identify a novel role for Foxp1 in controlling HFSC proliferation with cellular dynamic location in response to oxidative stress during hair cycling.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Hanjun
authors.initials: H
authors.lastname: Li
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Rujiang
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
authors.affiliation: Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Dekker
authors.affiliation: Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Haley O
authors.initials: HO
authors.lastname: Tucker
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Zhengju
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Xizhi
authors.initials: X
authors.lastname: Guo
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018859:Hair Follicle / Q000166:cytology* / Q000254:growth & development*; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D013234:Stem Cells / Q000166:cytology*; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D013879:Thioredoxins