MassIVE MSV000083949

Imported Reanalysis Dataset Public PXD002428

DDX3Y and other Male Specific Region of Y Chromosome Genes may modulate neuronal differentiation and mediate various biological pathways in addition to their well described role regulating spermatogenesis

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Description

Human tissue based proteomics projects are challenging due to low abundance of proteins and tissue specificity of protein expression. In this study, we aimed to develop a cell-based approach to profile the male specific region of the Y chromosome (MSY) proteins. First, we profiled the expression of 23 Y chromosome genes and 15 of their X-linked homologues during neural cell differentiation from NT2 cells at three different developmental stages using qRT-PCR, western blotting and immunofluorescent (IF) techniques. The expression level of 12 Y-linked genes significantly increased over neural differentiation. Including RBMY1, EIF1AY, DDX3Y1, HSFY1, BPY2, PCDH11Y, UTY, RPS4Y1, USP9Y, SRY, PRY, and ZFY. Subsequently, DDX3Y was selected as a candidate for knockdown as it was significantly expressed in neural progenitor cells and it is known to be expressed in a gender specific manner and play a role in spermatogenesis. A siRNA-mediated DDX3Y knockdown 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 920 reproducibly identified proteins detected, 74 proteins were differentially expressed following DDX3Y siRNA treatment compared to mock treated cells. Functional grouping indicated these proteins were associated with cell cycle, cell-to-cell signaling, apoptosis and other important networks such as RNA processing and transcription regulation. Disease-based analysis confirmed DDX3Y involvement primarily in neurological and RNA metabolism disorders. Our results confirm that MSY genes are expressed in male neuronal cells, and demonstrate that Y linked DDX3 (DDX3Y) could play a multifunctional role in neural cell development in a sexually dimorphic manner. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Chromosome Centric Human Proteome Project (C-HPP) ; Cell-based Human Proteome Project ; Y-linked genes ; DDX3Y ; Shotgun Proteomics ; Apoptosis ; Cell Cycle ; RNA metabolism.

Contact

Principal Investigators:
(in alphabetical order) 		Ghasem Hosseini Salekdeh, Royan Institute-Tehran, Iran, N/A
Submitting User: ccms

Publications

Vakilian H, Mirzaei M, Sharifi Tabar M, Pooyan P, Habibi Rezaee L, Parker L, Haynes PA, Gourabi H, Baharvand H, Salekdeh GH.
DDX3Y, a Male-Specific Region of Y Chromosome Gene, May Modulate Neuronal Differentiation.
J. Proteome Res. 2015 Sep 4;14(9):3474-83. Epub 2015 Jul 22.

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