Y chromosome genes may play roles in the development of neural rosettes from human embryonic stem cells

Farzaneh Khani, Simin Nafian, Sepideh Mollamohammadi, Shiva Nemati, Bahare Shokoohian, Seyedeh Nafiseh Hassani, Hossein Baharvand, Hamid Reza Soleimanpour-lichaei*, Ghasem Hosseini Salekdeh*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)

    Abstract

    Background: The human Y chromosome harbors genes that are mainly involved in the growth, development, sexual dimorphism, and spermatogenesis process. Despite many studies, the function of the male-specific region of the Y chromosome (MSY) awaits further clarification, and a cell-based approach can help in this regard. 

    Results: In this study, we have developed four stable transgenic male embryonic stem cell (ESCs) lines that can overexpress male-specific genes HSFY1, RBMY1A1, RPS4Y1, and SRY. As a proof of principle, we differentiated one of these cell lines (RPS4Y1 over-expressing ESCs) to the neural stem cell (rosette structure) and characterized them based on the expression level of lineage markers. RPS4Y1 expression in the Doxycycline-treated group was significantly higher than control groups at transcript and protein levels. Furthermore, we found Doxycycline-treated group had a higher differentiation efficiency than the untreated control groups. 

    Conclusions: Our results suggest that the RPS4Y1 gene may play a critical role in neurogenesis. Also, the generated transgenic ESC lines can be widely employed in basic and preclinical studies, such as sexual dimorphism of neural and cardiac functions, the development of cancerous and non-cancerous disease models, and drug screening. 

    Graphical Abstract: [Figure not available: see fulltext.].

    Original languageEnglish
    Pages (from-to)3008-3020
    Number of pages13
    JournalStem Cell Reviews and Reports
    Volume18
    Issue number8
    Early online date3 Jun 2022
    DOIs
    Publication statusPublished - Dec 2022

    Keywords

    • Human Embryonic Stem Cells (hESC)
    • Neural differentiation
    • RPS4Y1
    • Stable cell line
    • Y-Chromosome Human Proteome Project (Y-HPP)

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