title: DDX3Y, a Male-Specific Region of Y Chromosome Gene, May Modulate Neuronal Differentiation.
abstract: Although it is apparent that chromosome complement mediates sexually dimorphic expression patterns of some proteins that lead to functional differences, there has been insufficient evidence following the manipulation of the male-specific region of the Y chromosome (MSY) gene expression during neural development. In this study, we profiled the expression of 23 MSY genes and 15 of their X-linked homologues during neural cell differentiation of NTERA-2 human embryonal carcinoma cell line (NT2) cells in three different developmental stages using qRT-PCR, Western blotting, and immunofluorescence. The expression level of 12 Y-linked genes significantly increased over neural differentiation, including RBMY1, EIF1AY, DDX3Y, HSFY1, BPY2, PCDH11Y, UTY, RPS4Y1, USP9Y, SRY, PRY, and ZFY. We showed that siRNA-mediated knockdown of DDX3Y, a DEAD box RNA helicase enzyme, in neural progenitor cells impaired cell cycle progression and increased apoptosis, consequently interrupting differentiation. Label-free quantitative shotgun proteomics based on a spectral counting approach was then used to characterize the proteomic profile of the cells after DDX3Y knockdown. Among 917 reproducibly identified proteins detected, 71 proteins were differentially expressed following DDX3Y siRNA treatment compared with mock treated cells. Functional grouping indicated that these proteins were involved in cell cycle, RNA splicing, and apoptosis, among other biological functions. Our results suggest that MSY genes may play an important role in neural differentiation and demonstrate that DDX3Y could play a multifunctional role in neural cell development, probably in a sexually dimorphic manner.
authors.affiliation: Department of Stem Cells Biology & Technology, Royan Institute , Banihashem Sq., Banihashem St., Ressalat highway, Tehran, Iran.
authors.forename: Haghighat
authors.initials: H
authors.lastname: Vakilian
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University , Sydney, New South Wales 2109, Australia.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mirzaei
authors.affiliation: Department of Stem Cells Biology & Technology, Royan Institute , Banihashem Sq., Banihashem St., Ressalat highway, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sharifi Tabar
authors.affiliation: Department of Stem Cells Biology & Technology, Royan Institute , Banihashem Sq., Banihashem St., Ressalat highway, Tehran, Iran.
authors.forename: Paria
authors.initials: P
authors.lastname: Pooyan
authors.affiliation: Department of Stem Cells Biology & Technology, Royan Institute , Banihashem Sq., Banihashem St., Ressalat highway, Tehran, Iran.
authors.forename: Lida
authors.initials: L
authors.lastname: Habibi Rezaee
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University , Sydney, New South Wales 2109, Australia.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Parker
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University , Sydney, New South Wales 2109, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Haynes
authors.affiliation: Department of Genetics at Reproductive Biomedicine Research Center, Royan Institute , Banihashem Sq., Banihashem St., Ressalat highway, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Gourabi
authors.affiliation: Department of Stem Cells Biology & Technology, Royan Institute , Banihashem Sq., Banihashem St., Ressalat highway, Tehran, Iran.|Department of Developmental Biology, University of Science and Culture , Sharif Esfahani Blvd, Park Street, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
authors.affiliation: Department of Stem Cells Biology & Technology, Royan Institute , Banihashem Sq., Banihashem St., Ressalat highway, Tehran, Iran.|Seed and Plant Improvement Institute's Campus, Agricultural Biotechnology Research Institute of Iran , Mahdasht Road, Karaj, Iran.
authors.forename: Ghasem Hosseini
authors.initials: GH
authors.lastname: Salekdeh
mesh_terms: D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D041322:Chromosomes, Human, Y; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D040901:Proteomics
chemical_list: D015778:Minor Histocompatibility Antigens; C492034:DDX3Y protein, human; D053487:DEAD-box RNA Helicases
keywords: Cell-Based Human Proteome Project; Chromosome-Centric Human Proteome Project (C-HPP); DDX3Y; RNA metabolism; Y-linked genes; apoptosis; cell cycle; shotgun proteomics